Study Of Letrozole With Or Without Palbociclib (PD-033299... | NCT00721409 | Trialant
NCT00721409
Sponsor
Pfizer
Status
Completed
Last Update Posted
Nov 4, 2019Actual
Enrollment
177Actual
Phase
Phase 2
Conditions
Breast Cancer
Interventions
PD 0332991
letrozole
letrozole
Countries
United States
Canada
France
Germany
Hungary
Ireland
Italy
Russia
South Africa
South Korea
Spain
Ukraine
Protocol Section
Identification Module
NCT ID
NCT00721409
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
A5481003
Secondary IDs
ID
Type
Description
Link
2008-002392-27
EudraCT Number
Brief Title
Study Of Letrozole With Or Without Palbociclib (PD-0332991) For The First-Line Treatment Of Hormone-Receptor Positive Advanced Breast Cancer
Official Title
PHASE 1/2, OPEN-LABEL, RANDOMIZED STUDY OF THE SAFETY, EFFICACY, AND PHARMACOKINETICS OF LETROZOLE PLUS PD 0332991 (ORAL CDK 4/6 INHIBITOR) AND LETROZOLE SINGLE AGENT FOR THE FIRST-LINE TREATMENT OF ER POSITIVE, HER2 NEGATIVE ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN
Acronym
Not provided
Organization
PfizerINDUSTRY
Status Module
Record Verification Date
Oct 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Sep 15, 2008Actual
Primary Completion Date
Nov 29, 2013Actual
Completion Date
Dec 20, 2017Actual
First Submitted Date
Jul 22, 2008
First Submission Date that Met QC Criteria
Jul 23, 2008
First Posted Date
Jul 24, 2008Estimated
Results Waived
Not provided
Results First Submitted Date
Mar 4, 2015
Results First Submitted that Met QC Criteria
Mar 4, 2015
Results First Posted Date
Mar 19, 2015Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Dec 5, 2014
Certification/Extension First Submitted that Passed QC Review
Dec 5, 2014
Certification/Extension First Posted Date
Dec 24, 2014Estimated
Last Update Submitted Date
Oct 21, 2019
Last Update Posted Date
Nov 4, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
PfizerINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The study is aimed to confirm that letrozole + PD 0332991 is safe and tolerable and to assess the effect of the combination on advanced breast cancer
Detailed Description
Not provided
Conditions Module
Conditions
Breast Cancer
Keywords
hormone-receptor positive advanced breast cancer
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
177Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Arm A
Experimental
letrozole + PD 0332991
Drug: PD 0332991
Drug: letrozole
Arm B
Active Comparator
letrozole
Drug: letrozole
Interventions
Name
Type
Description
Arm Group Labels
Other Names
PD 0332991
Drug
125 mg/d capsules orally for 3 out of 4 weeks in repeated cycles
Arm A
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Maximum treatment duration (approximately 55 months)
Number of Participants With Treatment-Related Adverse Events at Phase 1
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Maximum treatment duration (approximately 55 months)
Number of Participants With Dose Limiting Toxicities at Phase 1
Dose limiting toxicity was defined as any of the following TEAEs occurring during the second cycle of treatment and possibly attributable to the combination of letrozole plus Palbociclib: 1. Grade 4 hematologic toxicity (including platelets <25,000/μL, ANC <500/μL). 2. Grade 3 neutropenia associated with a documented infection or fever ≥38.5°C. 3. Grade ≥3 non-hematologic toxicities, except those that have not been maximally treated (eg, nausea, vomiting, diarrhea, hypertension). 4. Delay by ≥1 week in receiving the next scheduled dose of either study treatment due to persisting treatment-related toxicities (platelet count <50,000/μL; ANC <1,000/μL; nonhematologic toxicities of Grade ≥3 severity). 5. Inability to deliver at least 80% of the planned Palbociclib or letrozole doses during Cycle 2 due to toxicity possibly attributable to the study treatment.
Cycle 2 (4 weeks)
Progression-Free Survival (PFS) at Phase 2 - Investigator Assessment
Secondary Outcomes
Measure
Description
Time Frame
Objective Response Rate - Percentage of Participants With Confirmed Objective Tumor Response at Phase 1
Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Inoperable estrogen receptor positive and HER2 negative breast cancer.
Postmenopausal status.
Tumor tissue (archived acceptable) available for biomarker studies. For Phase 2 Part 2 - CCND1 amplification and/or loss of p16 as determined by the central laboratory.
Acceptable bone marrow, liver and kidney function.
Exclusion Criteria:
Prior or concomitant treatment for advanced breast cancer.
Other major cancer in the past 3 years.
Important cardiovascular events in the past 6 months.
Finn RS, Rugo HS, Gelmon KA, Cristofanilli M, Colleoni M, Loi S, Schnell P, Lu DR, Theall KP, Mori A, Gauthier E, Bananis E, Turner NC, Dieras V. Long-Term Pooled Safety Analysis of Palbociclib in Combination with Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Updated Analysis with up to 5 Years of Follow-Up. Oncologist. 2021 May;26(5):e749-e755. doi: 10.1002/onco.13684. Epub 2021 Mar 10.
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Phase 2 portion has 2 parts. Phase 2, Part 1 - ER positive, HER2 negative postmenopausal women with advanced breast cancer. Phase 2, Part 2- ER positive, HER2 negative postmenopausal women with tumors demonstrating CCND1 gene amplification and/or loss of CDKN2A gene.
Recruitment Details
This Phase 1/2, open-label, randomized study enrolled a total of 12 participants at 3 sites in the United States for Phase 1. Phase 1 participants received Palbociclib + Letrozole. In Phase 2, a total of 165 participants were randomized (84 in palbociclib plus letrozole arm and 81 in letrozole alone arm) at 50 sites in 12 countries.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Phase 1 (Palbociclib + Letrozole)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Australia
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Not provided
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
letrozole
Drug
2.5 mg/d tablets orally on a continuous regimen
Arm A
letrozole
Drug
2.5 mg/d tablets orally on a continuous regimen
Arm B
PFS was defined as the time from randomization (or the first dose of study treatment for non-randomized studies) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PFS calculated as (Weeks or Months) = (first event date minus randomization or the first dose date plus 1) divided by 7 (or 30.44 if in months). PFS is usually characterized by the median, 25% percentile,75% percentile and their 95% Confidence Intervals (CIs).
From randomization date to date of first documentation of progression or death (assessed up to 41 months)
From Baseline up to end of study (assessed up to 55 months)
Percentage of Participants With Clinical Benefit Response (CBR) at Phase 1
CBR is defined as a confirmed CR, confirmed PR, or stable disease (SD) for at least 24 weeks on study according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 weeks after initial response.
From Baseline up to end of study (assessed up to 55 months)
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC24) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Maximum Observed Plasma Concentration (Cmax) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Time to Maximum Plasma Concentration (Tmax) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Terminal Plasma Half-life (t1/2) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Clearance (CL/F) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Volume of Distribution (Vz/F) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: AUC24 at Phase 1
On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
Cycle 2 Day 14, Cycle 2 Day 28
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Cmax at Phase 1
On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
Cycle 2 Day 14, and Cycle 2 Day 28
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Tmax at Phase 1
On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
Cycle 2 Day 14, and Cycle 2 Day 28
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Participants with maximum increase from baseline of 30 to less than (<) 60 msec(borderline) and greater than or equal to (>=) 60 msec (prolonged) were summarized.
Cycle 1 Day 1 prior to dosing, Cycle 1 Day 14 (2, 4 [prior to meal], 8, 24, 48, and 96 hours after dosing of Palbociclib), Cycle 2 Day 1 and Day 14 (prior to and 4 hours after dosing of letrozole)
Overall Survival (OS) at Phase 2
Time in weeks or months from randomization to date of death due to any cause. OS was calculated as (the death date or last known alive date (if death date unavailable) minus the date of randomization plus 1) divided by 7 or 30.44 if in months.
From randomization until death (assessed up to 86 months)
Objective Response Rate - Percentage of Participants With Confirmed Objective Response at Phase 2- Investigator Assessment
Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
From randomization up to the end of treatment (approximately 41 months)
Objective Response Rate - Percentage of Participants With Confirmed Objective Response in Participants With Measurable Disease at Phase 2- Investigator Assessment
Percentage of participants with objective response based assessment of confirmed CR or PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions. Measurable disease referred to the lesions that was accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques or as ≥10-16 mm with spiral computer tomography scan (depending on reconstruction interval). Clinical lesions were only be considered measurable when they were superficial (eg, skin nodules, palpable lymph nodes).
From randomization up to the end of treatment (approximately 41 months)
Duration of Response at Phase 2 - Investigator Assessment
Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization [or first dose of study medication for non-randomized studies] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per RECIST).
From randomization up to the end of treatment (approximately 41 months)
Number of Participants With CBR at Phase 2 - Investigator Assessment
CBR is defined as a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 24 weeks on study according to RECIST.
From randomization up to the end of treatment (approximately 41 months)
Time to Tumor Progression (TTP) at Phase 2-Investigator Assessment
Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization [or first dose of study medication for non-randomized studies] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per RECIST).
From randomization up to the end of treatment (approximately 41 months)
Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2
The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").
Baseline, End of treatment (approximately 41 months)
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2
The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").
Baseline, End of treatment (approximately 41 months)
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - p16/INK4A, CCND1
Tissue samples were used for retrospective biomarker analyses. For Phase 2 Part 2, the tissue samples were sent to a central laboratory for the assessment of participant selection biomarkers. For Phase 2 Part 1, the assessment of the biomarkers (CCND1 amplification and/or loss of p16) were performed retrospectively from the available samples.
Screening visit (≤ 28 Days prior to dosing)
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Ki67
Frequency of tumor tissue biomarker Ki67 was evaluated in across treatment groups.
Screening visit (≤ 28 Days prior to dosing)
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1
Presence or absence of tumor RB and CyclinD1 were evaluated. The following definitions of expression applied in the below table: Positive: any expression >0 and Negative: any expression=0.
Screening visit (≤ 28 Days prior to dosing)
Summary of Copy Number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) at Phase 2
Gene copy number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) were evaluated. This analysis was done for Phase 2 combined group.
Screening visit (≤ 28 Days prior to dosing)
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2
One 2-mL blood specimen was collected for the analysis of germline polymorphism in CYP19A1 and CCND1 genes. A single nucleotide polymorphism (SNP) rs4646 as defined in the National Center for Biotechnology Information (NCBI) database in the aromatase gene (CYP19A1) was analyzed. A germline polymorphism G/A870 (rs9344) in the CCND1 gene was analyzed.
Screening visit (≤ 28 Days prior to dosing)
Number of Participants With TEAEs (All Causalities) at Phase 2
AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.AEs included both serious and non-serious AEs.SAE:AE resulting in any of following outcomes/deemed significant and jeopardized participants or required treatment to prevent other AE outcomes for any other reason:death;initial or prolonged inpatient hospitalization;life-threatening experience (immediate risk of dying);persistent or significant disability/incapacity;congenital anomaly.Treatment emergent AEs:events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or worsened relative to pre-treatment state.AEs were graded as per the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and coded using Medical Dictionary for Regulatory Activities (MedDRA). Participants with AE of grade 3 or 4 and grade 5 were reported as Grade 3:Severe, Grade 4:Life threatening, Grade 5:Death related to AE.
Baseline up to 28 days after last dose of study drug (for a maximum of 86 months)
Number of Participants With Treatment-Related Adverse Events at Phase 2
AE: any untoward medical occurrence in a participant who received study drug. AEs included both serious and non-serious adverse events. SAE: AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent AEs: events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Treatment related AEs: all AEs with causality related to treatment. Relatedness to drug was assessed by the investigator. AEs were graded according to the CTCAE version 3.0 and coded using the MedDRA. Number of participants with AE of grade 3 or 4 and with AE of grade 5 were reported as Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE.
Baseline up to 28 days after last dose of study drug (for a maximum of 86 months)
Alhambra
California
91801
United States
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
Bakersfield
California
93309
United States
St. Joseph Heritage Healthcare
Fullerton
California
92835
United States
UCLA West Medical Pharmacy (Drug Management Only)
Los Angeles
California
90095-1772
United States
UCLA West Medical Pharmacy
Los Angeles
California
90095-1772
United States
Ronald Reagan UCLA Medical Center
Los Angeles
California
90095-6984
United States
UCLA West Medical Pharmacy
Los Angeles
California
90095-7349
United States
Drug Management Only: UCLA West Medical Pharmacy
Los Angeles
California
90095
United States
Drug Management Only
Los Angeles
California
90095
United States
Regulatory Managment
Los Angeles
California
90095
United States
Ronald Reagan UCLA Medical Center
Los Angeles
California
90095
United States
TORI -US Central Administration (Regulatory Management)
Los Angeles
California
90095
United States
TORI -US Central Administration
Los Angeles
California
90095
United States
TORI Central Administration (Regulatory Management)
Los Angeles
California
90095
United States
TORI Central Administration (Regulatory Managment Only)
Los Angeles
California
90095
United States
TRIO-US Central Administration
Los Angeles
California
90095
United States
UCLA Hematology/Oncology
Los Angeles
California
90095
United States
UCLA, Hematology/Oncology
Los Angeles
California
90095
United States
Westwood Bowyer Clinic, Peter Morton Medical Building
Los Angeles
California
90095
United States
Central Hematology Oncology Medical Group, Inc
Pasadena
California
91107
United States
Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates
Redondo Beach
California
90277
United States
Sansum Santa Barbara Medical Foundation Clinic
Santa Barbara
California
93105
United States
Central Coast Medical Oncology Corporation
Santa Maria
California
93454
United States
Santa Monica-UCLA Medical Center and Orthopaedic Hospital
Santa Monica
California
90404
United States
UCLA Hematology Oncology-Santa Monica
Santa Monica
California
90404
United States
UCLA Hematology/Oncology - Santa Clarita
Valencia
California
91355
United States
Gwinnett Hospital System Inc.-d/b/a-The Center for Cancer Care
Duluth
Georgia
30096
United States
Gwinnett Hospital System Inc.-d/b/a-The Center for Cancer Care
Lawrenceville
Georgia
30046
United States
Gwinnett Hospital System Inc.-d/b/a-The Center for Cancer Care
Snellville
Georgia
30078
United States
Illinois Cancer Specialists
Chicago
Illinois
60611
United States
Resurrection Medical Group
Chicago
Illinois
60657
United States
North Shore Oncology-Hematology Associates
Crystal Lake
Illinois
60014
United States
North Shore Hematology Oncology
Highland Park
Illinois
60035
United States
North Shore Oncology-Hematology Associates
Libertyville
Illinois
60048
United States
North Shore Hematology Oncology
Skokie
Illinois
60077
United States
Regulatory Office: Comprehensive Cancer Centers of Nevada
Henderson
Nevada
89014
United States
Comprehensive Cancer Centers of Nevada
Henderson
Nevada
89052
United States
Comprehensive Cancer Centers of Nevada
Henderson
Nevada
89074
United States
Comprehensive Cancer Centers of Nevada
Las Vegas
Nevada
89128
United States
Comprehensive Cancer Centers of Nevada
Las Vegas
Nevada
89148
United States
Comprehensive Cancer Centers of Nevada
Las Vegas
Nevada
89169
United States
Texas Oncology-Dallas Presbyterian Hospital
Dallas
Texas
75231
United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas
Texas
75246
United States
Investigational Products Center (IPC)
Fort Worth
Texas
76177
United States
US Oncology Research and Clinical Pharmacy
Fort Worth
Texas
76177
United States
Virginia Cancer Specialists, PC
Arlington
Virginia
22205
United States
Virginia Cancer Specialists, PC
Fairfax
Virginia
22031
United States
Virginia Cancer Specialists, PC
Gainesville
Virginia
20155
United States
Virginia Cancer Specialists, PC
Leesburg
Virginia
20176
United States
Virginia Cancer Specialists, PC
Woodbridge
Virginia
22191
United States
BC Cancer Agency - Vancouver Centre
Vancouver
British Columbia
V5Z 4E6
Canada
CSSS Champlain-Charles-Le Moyne Local HS-0054
Greenfield Park
Quebec
J4V 2H1
Canada
Centre Paul Papin, CRLCC
Angers
49933
France
CHD Vendee
La Roche-sur-Yon
85925
France
Gemeinschaftspraxis, Onkologischer Schwerpunkt am Oskar-Helene-Heim
Berlin
14195
Germany
Gemeinschaftspraxis Haematologie-Onkologie
Dresden
01307
Germany
Martin-Luther-Universitaet Halle-Wittenberg
Halle
06097
Germany
Universitaetsklinik und Poliklinik fuer Gynaekologie, Martin-Luther-Universitaet Halle-Wittenberg
Halle
06120
Germany
Nationales Centrum fuer Tumorerkrankungen
Heidelberg
69120
Germany
Frauenaerzte Pruener Gang Abts & Partner
Kiel
24103
Germany
Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe Universitaetsklinik Mainz
Mainz
55101
Germany
Onkolog. Gemeinschaftspraxis
München
80335
Germany
Frauenklinik vom Roten Kreuz
München
80637
Germany
Frauenklinik und Poliklinik Klinikum rechts der Isar, Technische Universitaet Muenchen
München
81675
Germany
Mutterhaus der Borromaeerinnen, Innere Medizin I
Trier
54290
Germany
Szent Margit Korhaz, Onkologia
Budapest
1032
Hungary
Orszagos Onkologiai Intezet, Kemoterapia B
Budapest
1122
Hungary
Fovarosi Onkormanyzat Uzsoki Utcai Korhaz
Budapest
1145
Hungary
Petz Aladar Megyei Oktato Korhaz, Onkoradiologia
Győr
9023
Hungary
Borsod-Abauj-Zemplen Megyei Korhaz és Egyetemi Oktato Korhaz, Onkologia
Miskolc
3526
Hungary
Szabolcs-Szatmar-Bereg Megyei Korhazak es
Nyíregyháza
4400
Hungary
Markusovszky Egyetemi Oktatokorhaz, Onkoradiologiai Osztaly
Szombathely
9700
Hungary
Bon Secours Hospital
Cork
Ireland
St. Vincent's University Hospital
Dublin
4
Ireland
Mater Misericordiae University Hospital
Dublin
7
Ireland
Mater Private Hospital
Dublin
7
Ireland
St. James's Hospital
Dublin
Ireland
Divisione Oncologia Medica Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRST
Meldola
FC
47014
Italy
M.O. di Oncologia - Azienda USL di Rimini - Ospedale "Cervesi"
Cattolica
47841
Italy
Ospedale Civile di Faenza Centro Oncologico
Faenza, RA
48018
Italy
Unita' Operativa di Oncologia, Ospedale Civile di Lugo
Lugo, RA
48022
Italy
Ospedale Civile di Ravenna
Ravenna
48100
Italy
Azienda Unita Sanitaria Locale di Rimini, U.O. di Oncologia ed Oncoematologia Ospedale degli Infermi
Rimini
47900
Italy
Ospedale Villa San Pietro
Roma
00189
Italy
Federal State Budgetary Scientific Institution
Moscow
115478
Russia
Pyatigorsk Oncology Center
Pyatigorsk
357502
Russia
State Budgetary Healthcare Institution "Samara Regional Clinical Oncology Dispensary"
Samara
443031
Russia
Republican Clinical Oncology Dispensary of the Ministry of Health of Bashkortostan Republic
Ufa
450054
Russia
Department of Oncotherapy, National Hospital
Bloemfontein
9301
South Africa
Eastleigh Breast Care Centre
Pretoria
0041
South Africa
National Cancer Center, Center for Breast Cancer
Goyang-si
Gyeonggi-do
10408
South Korea
Seoul National University Hospital
Seoul
03080
South Korea
Samsung Medical Center
Seoul
135-710
South Korea
Ico-Hospitalet
L'Hospitalet de Llobregat
Barcelona
08907
Spain
Centro Oncologico de Galicia
A Coruña
15009
Spain
Hospital General Universitario Vall D'Hebron
Barcelona
08035
Spain
Hospital Universitario 12 de Octubre
Madrid
28041
Spain
Hospital Universitario Virgen Del Rocio
Seville
41013
Spain
Department of Oncology and Medical Radiology, SI "DMA of MOH, Ukraine, "MI "Dnipropetrovsk City
Dnipropetrovsk
49102
Ukraine
Municipal Treatment-and-Prophylactic Institution 'Donetsk City Oncological Dispensary' Radiology dep
Donetsk
83087
Ukraine
Municipal clinical treatment-and-propyilactic institution "Donetsk regional oncology center',
Donetsk
83092
Ukraine
Kyiv City Clinical Oncologic Center
Kyiv
03115
Ukraine
Lviv State Oncologic Regional Treatment and Diagnostic Centre
Lviv
79031
Ukraine
Derived
Finn RS, Boer K, Bondarenko I, Patel R, Pinter T, Schmidt M, Shparyk YV, Thummala A, Voitko N, Bananis E, McRoy L, Wilner K, Huang X, Kim S, Slamon DJ, Ettl J. Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (PALOMA-1, TRIO-18). Breast Cancer Res Treat. 2020 Sep;183(2):419-428. doi: 10.1007/s10549-020-05755-7. Epub 2020 Jul 18.
Ettl J, Im SA, Ro J, Masuda N, Colleoni M, Schnell P, Bananis E, Lu DR, Cristofanilli M, Rugo HS, Finn RS. Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies. Breast Cancer Res. 2020 Mar 12;22(1):27. doi: 10.1186/s13058-020-01263-0.
Rugo HS, Turner NC, Finn RS, Joy AA, Verma S, Harbeck N, Masuda N, Im SA, Huang X, Kim S, Sun W, Iyer S, Schnell P, Bartlett CH, Johnston S. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018 Sep;101:123-133. doi: 10.1016/j.ejca.2018.05.017. Epub 2018 Jul 25.
Dieras V, Rugo HS, Schnell P, Gelmon K, Cristofanilli M, Loi S, Colleoni M, Lu DR, Mori A, Gauthier E, Huang Bartlett C, Slamon DJ, Turner NC, Finn RS. Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer. J Natl Cancer Inst. 2019 Apr 1;111(4):419-430. doi: 10.1093/jnci/djy109.
Wedam SB, Beaver JA, Amiri-Kordestani L, Bloomquist E, Tang S, Goldberg KB, Sridhara R, Ibrahim A, Kim G, Kluetz P, McKee A, Pazdur R. US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments. J Clin Oncol. 2018 Apr 20;36(12):1225-1231. doi: 10.1200/JCO.2017.74.6917. Epub 2018 Mar 9.
Bell T, Crown JP, Lang I, Bhattacharyya H, Zanotti G, Randolph S, Kim S, Huang X, Huang Bartlett C, Finn RS, Slamon D. Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as first-line treatment. Curr Med Res Opin. 2016 May;32(5):959-65. doi: 10.1185/03007995.2016.1157060. Epub 2016 Mar 2.
Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16.
FG001
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
FG002
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
FG00012 subjects
FG00184 subjects
FG00281 subjects
Treated
FG00012 subjects
FG00183 subjects
FG00277 subjects
COMPLETED
FG0000 subjects
FG0012 subjects
FG0022 subjects
NOT COMPLETED
FG00012 subjects
FG00182 subjects
FG00279 subjects
Type
Comment
Reasons
Global deterioration of health status
FG0002 subjects
FG0016 subjects
FG0023 subjects
Death
FG0000 subjects
FG0011 subjects
FG0020 subjects
Randomized not Treated
FG0000 subjects
FG0011 subjects
FG0024 subjects
Reason not specified
FG0001 subjects
FG0010 subjects
FG0022 subjects
Adverse Event
FG0000 subjects
FG00113 subjects
FG0022 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0021 subjects
Withdrawal by Subject
FG0001 subjects
FG0016 subjects
FG0025 subjects
Objective progression or relapse
FG0008 subjects
FG00155 subjects
FG00262 subjects
Analysis was done on participants who received at least one dose of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Phase 1 (Palbociclib + Letrozole)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
BG001
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
BG002
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00012
BG00184
BG00281
BG003177
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
<18 Years
Title
Measurements
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00012
BG00184
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Safety analysis set included all participants who received at least 1 dose of any agent of the combination.
Posted
Number
Participants
Maximum treatment duration (approximately 55 months)
ID
Title
Description
OG000
Phase 1 (Palbociclib + Letrozole)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Units
Counts
Participants
OG00012
Title
Denominators
Categories
Participants with AEs
Title
Measurements
OG00012
Participants with SAEs
Title
Measurements
OG0002
Participants with Grade 3 or 4 AEs
Primary
Number of Participants With Treatment-Related Adverse Events at Phase 1
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Safety analysis set included all participants who received at least 1 dose of any agent of the combination.
Posted
Number
Participants
Maximum treatment duration (approximately 55 months)
ID
Title
Description
OG000
Phase 1 (Palbociclib + Letrozole)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Units
Counts
Participants
OG000
Primary
Number of Participants With Dose Limiting Toxicities at Phase 1
Dose limiting toxicity was defined as any of the following TEAEs occurring during the second cycle of treatment and possibly attributable to the combination of letrozole plus Palbociclib: 1. Grade 4 hematologic toxicity (including platelets <25,000/μL, ANC <500/μL). 2. Grade 3 neutropenia associated with a documented infection or fever ≥38.5°C. 3. Grade ≥3 non-hematologic toxicities, except those that have not been maximally treated (eg, nausea, vomiting, diarrhea, hypertension). 4. Delay by ≥1 week in receiving the next scheduled dose of either study treatment due to persisting treatment-related toxicities (platelet count <50,000/μL; ANC <1,000/μL; nonhematologic toxicities of Grade ≥3 severity). 5. Inability to deliver at least 80% of the planned Palbociclib or letrozole doses during Cycle 2 due to toxicity possibly attributable to the study treatment.
Safety analysis set included all participants who received at least 1 dose of any agent of the combination.
Posted
Number
Participants
Cycle 2 (4 weeks)
ID
Title
Description
OG000
Phase 1 (Palbociclib + Letrozole)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Primary
Progression-Free Survival (PFS) at Phase 2 - Investigator Assessment
PFS was defined as the time from randomization (or the first dose of study treatment for non-randomized studies) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PFS calculated as (Weeks or Months) = (first event date minus randomization or the first dose date plus 1) divided by 7 (or 30.44 if in months). PFS is usually characterized by the median, 25% percentile,75% percentile and their 95% Confidence Intervals (CIs).
Intent-to-Treat (ITT) was used. This represented all randomized participants from Ph2P1 or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.
Posted
Median
95% Confidence Interval
Months
From randomization date to date of first documentation of progression or death (assessed up to 41 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
Secondary
Objective Response Rate - Percentage of Participants With Confirmed Objective Tumor Response at Phase 1
Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
Efficacy analysis set included all enrolled participants with the disease under study, adequate baseline disease assessment, and who started study treatment.
Posted
Number
95% Confidence Interval
Percentage of participants
From Baseline up to end of study (assessed up to 55 months)
ID
Title
Description
OG000
Phase 1 (Palbociclib + Letrozole)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Units
Counts
Secondary
Percentage of Participants With Clinical Benefit Response (CBR) at Phase 1
CBR is defined as a confirmed CR, confirmed PR, or stable disease (SD) for at least 24 weeks on study according to RECIST. Confirmed responses are those that persisted on repeat imaging >= 4 weeks after initial response.
Efficacy analysis set included all enrolled participants with the disease under study, adequate baseline disease assessment, and who started study treatment.
Posted
Number
95% Confidence Interval
Percentage of participants
From Baseline up to end of study (assessed up to 55 months)
ID
Title
Description
OG000
Phase 1 (Palbociclib + Letrozole)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Units
Counts
Participants
OG000
Secondary
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC24) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng·hr/mL
Cycle 1 Day 14, and Cycle 2 Day 14
ID
Title
Description
OG000
Palbociclib Alone (Cycle 1 Day 14)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment.
OG001
Palbociclib + Letrozole (Cycle 2 Day 14)
In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Secondary
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Maximum Observed Plasma Concentration (Cmax) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Cycle 1 Day 14, and Cycle 2 Day 14
ID
Title
Description
OG000
Palbociclib Alone (Cycle 1 Day 14)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment.
OG001
Palbociclib + Letrozole (Cycle 2 Day 14)
In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Secondary
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Time to Maximum Plasma Concentration (Tmax) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.
Posted
Median
Full Range
Hour
Cycle 1 Day 14, and Cycle 2 Day 14
ID
Title
Description
OG000
Palbociclib Alone (Cycle 1 Day 14)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment.
OG001
Palbociclib + Letrozole (Cycle 2 Day 14)
In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Secondary
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Terminal Plasma Half-life (t1/2) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.
Posted
Mean
Standard Deviation
Hour
Cycle 1 Day 14, and Cycle 2 Day 14
ID
Title
Description
OG000
Palbociclib Alone (Cycle 1 Day 14)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment.
OG001
Palbociclib + Letrozole (Cycle 2 Day 14)
In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Secondary
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Clearance (CL/F) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.
Posted
Geometric Mean
Geometric Coefficient of Variation
L/hr
Cycle 1 Day 14, and Cycle 2 Day 14
ID
Title
Description
OG000
Palbociclib Alone (Cycle 1 Day 14)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment.
OG001
Palbociclib + Letrozole (Cycle 2 Day 14)
In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Secondary
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Volume of Distribution (Vz/F) at Phase 1
On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.
Posted
Geometric Mean
Geometric Coefficient of Variation
L
Cycle 1 Day 14, and Cycle 2 Day 14
ID
Title
Description
OG000
Palbociclib Alone (Cycle 1 Day 14)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment.
OG001
Palbociclib + Letrozole (Cycle 2 Day 14)
In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Secondary
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: AUC24 at Phase 1
On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng·hr/mL
Cycle 2 Day 14, Cycle 2 Day 28
ID
Title
Description
OG000
Palbociclib + Letrozole (Cycle 2 Day 14)
Participants received 125 mg oral doses of palbociclib with daily 2.5 mg doses of letrozole.
OG001
Letrozole Alone (Cycle 2 Day 28)
Participants received daily 2.5 mg doses of letrozole alone.
Units
Counts
Secondary
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Cmax at Phase 1
On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Cycle 2 Day 14, and Cycle 2 Day 28
ID
Title
Description
OG000
Palbociclib + Letrozole (Cycle 2 Day 14)
Participants received 125 mg oral doses of palbociclib with daily 2.5 mg doses of letrozole.
OG001
Letrozole Alone (Cycle 2 Day 28)
Participants received daily 2.5 mg doses of letrozole alone.
Units
Counts
Secondary
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Tmax at Phase 1
On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
The pharmacokinetic concentration set included all participants who were treated and had at least 1 concentration measurement in at least 1 pharmacokinetic assessment day. The pharmacokinetic parameter analysis set consisted of all participants treated who had at least 1 of the pharmacokinetic parameters of primary interest.
Posted
Median
Full Range
Hour
Cycle 2 Day 14, and Cycle 2 Day 28
ID
Title
Description
OG000
Palbociclib + Letrozole (Cycle 2 Day 14)
Participants received 125 mg oral doses of palbociclib with daily 2.5 mg doses of letrozole.
OG001
Letrozole Alone (Cycle 2 Day 28)
Participants received daily 2.5 mg doses of letrozole alone.
Units
Counts
Participants
Secondary
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Participants with maximum increase from baseline of 30 to less than (<) 60 msec(borderline) and greater than or equal to (>=) 60 msec (prolonged) were summarized.
Safety analysis set included all participants who received at least 1 dose of any agent of the combination.
Posted
Number
Participants
Cycle 1 Day 1 prior to dosing, Cycle 1 Day 14 (2, 4 [prior to meal], 8, 24, 48, and 96 hours after dosing of Palbociclib), Cycle 2 Day 1 and Day 14 (prior to and 4 hours after dosing of letrozole)
ID
Title
Description
OG000
Phase 1 (Palbociclib + Letrozole)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
Secondary
Overall Survival (OS) at Phase 2
Time in weeks or months from randomization to date of death due to any cause. OS was calculated as (the death date or last known alive date (if death date unavailable) minus the date of randomization plus 1) divided by 7 or 30.44 if in months.
ITT was used. This represented all randomized participants from Ph2P1or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.
Posted
Median
95% Confidence Interval
Months
From randomization until death (assessed up to 86 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
Secondary
Objective Response Rate - Percentage of Participants With Confirmed Objective Response at Phase 2- Investigator Assessment
Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
ITT was used. This represented all randomized participants from Ph2P1or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.
Posted
Number
95% Confidence Interval
Percentage of participants
From randomization up to the end of treatment (approximately 41 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
Secondary
Objective Response Rate - Percentage of Participants With Confirmed Objective Response in Participants With Measurable Disease at Phase 2- Investigator Assessment
Percentage of participants with objective response based assessment of confirmed CR or PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions. Measurable disease referred to the lesions that was accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques or as ≥10-16 mm with spiral computer tomography scan (depending on reconstruction interval). Clinical lesions were only be considered measurable when they were superficial (eg, skin nodules, palpable lymph nodes).
Participants in ITT population with measurable disease were used.
Posted
Number
95% Confidence Interval
Percentage of participants
From randomization up to the end of treatment (approximately 41 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
Secondary
Duration of Response at Phase 2 - Investigator Assessment
Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization [or first dose of study medication for non-randomized studies] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per RECIST).
A subset of ITT population i.e., participants who had response was used for this analysis.
Posted
Median
95% Confidence Interval
Months
From randomization up to the end of treatment (approximately 41 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
Secondary
Number of Participants With CBR at Phase 2 - Investigator Assessment
CBR is defined as a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 24 weeks on study according to RECIST.
ITT was used. This represented all randomized patients from Ph2P1or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.
Posted
Number
95% Confidence Interval
Percentage of participants
From randomization up to the end of treatment (approximately 41 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
Secondary
Time to Tumor Progression (TTP) at Phase 2-Investigator Assessment
Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization [or first dose of study medication for non-randomized studies] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per RECIST).
ITT was used. This represented all randomized participants from Ph2P1or Ph2P2 or Ph2P1+Ph2P2, where participants were classified according to the randomized treatment regardless of what treatment, if any, was received.
Posted
Median
95% Confidence Interval
Months
From randomization up to the end of treatment (approximately 41 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
Secondary
Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2
The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").
Patient reported outcome evaluable participants included participants who had received at least 1 dose of study medication, had baseline data, and at least one post-baseline measurement.
Posted
Mean
Standard Error
Units on a scale
Baseline, End of treatment (approximately 41 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
Secondary
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2
The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").
Patient reported outcome evaluable participants included participants who had received at least 1 dose of study medication, had baseline data, and at least one post-baseline measurement.
Posted
Mean
Standard Error
Units on a scale
Baseline, End of treatment (approximately 41 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
Secondary
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - p16/INK4A, CCND1
Tissue samples were used for retrospective biomarker analyses. For Phase 2 Part 2, the tissue samples were sent to a central laboratory for the assessment of participant selection biomarkers. For Phase 2 Part 1, the assessment of the biomarkers (CCND1 amplification and/or loss of p16) were performed retrospectively from the available samples.
Copy number analysis set included participants in the Safety Analysis Set who had at least 1 of the biomarker assessments.
Posted
Number
Participants
Screening visit (≤ 28 Days prior to dosing)
ID
Title
Description
OG000
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG002
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
Secondary
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Ki67
Frequency of tumor tissue biomarker Ki67 was evaluated in across treatment groups.
All participants in the Safety Analysis set who had a Ki67 protein biomarker assessment.
Posted
Number
Participants
Screening visit (≤ 28 Days prior to dosing)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
Secondary
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1
Presence or absence of tumor RB and CyclinD1 were evaluated. The following definitions of expression applied in the below table: Positive: any expression >0 and Negative: any expression=0.
Protein biomarkers analysis set included all participants in the safety analysis set who had at least protein biomarker assessment.
Posted
Number
Participants
Screening visit (≤ 28 Days prior to dosing)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
Secondary
Summary of Copy Number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) at Phase 2
Gene copy number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) were evaluated. This analysis was done for Phase 2 combined group.
Copy number analysis set included participants in the Safety Analysis Set who had at least 1 of the biomarker assessments.
Posted
Mean
Standard Deviation
Copy number
Screening visit (≤ 28 Days prior to dosing)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
Units
Counts
Participants
Secondary
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2
One 2-mL blood specimen was collected for the analysis of germline polymorphism in CYP19A1 and CCND1 genes. A single nucleotide polymorphism (SNP) rs4646 as defined in the National Center for Biotechnology Information (NCBI) database in the aromatase gene (CYP19A1) was analyzed. A germline polymorphism G/A870 (rs9344) in the CCND1 gene was analyzed.
Polymorphism analysis set included participants in the safety analysis set who had at least 1 polymorphism assessment.
Posted
Number
Percentage of participants
Screening visit (≤ 28 Days prior to dosing)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Secondary
Number of Participants With TEAEs (All Causalities) at Phase 2
AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.AEs included both serious and non-serious AEs.SAE:AE resulting in any of following outcomes/deemed significant and jeopardized participants or required treatment to prevent other AE outcomes for any other reason:death;initial or prolonged inpatient hospitalization;life-threatening experience (immediate risk of dying);persistent or significant disability/incapacity;congenital anomaly.Treatment emergent AEs:events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or worsened relative to pre-treatment state.AEs were graded as per the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and coded using Medical Dictionary for Regulatory Activities (MedDRA). Participants with AE of grade 3 or 4 and grade 5 were reported as Grade 3:Severe, Grade 4:Life threatening, Grade 5:Death related to AE.
All treated as treated set included all treated participants classified by the treatment actually received.
Posted
Count of Participants
Participants
Baseline up to 28 days after last dose of study drug (for a maximum of 86 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
Secondary
Number of Participants With Treatment-Related Adverse Events at Phase 2
AE: any untoward medical occurrence in a participant who received study drug. AEs included both serious and non-serious adverse events. SAE: AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent AEs: events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Treatment related AEs: all AEs with causality related to treatment. Relatedness to drug was assessed by the investigator. AEs were graded according to the CTCAE version 3.0 and coded using the MedDRA. Number of participants with AE of grade 3 or 4 and with AE of grade 5 were reported as Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE.
All treated as treated set included all treated participants classified by the treatment actually received.
Posted
Count of Participants
Participants
Baseline up to 28 days after last dose of study drug (for a maximum of 86 months)
ID
Title
Description
OG000
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
Time Frame
Baseline up to 28 days after last dose of study drug (for a maximum of 86 months)
Description
An event may be categorized as serious in one participant and non serious in another participant, or one participant may experience both serious and non serious event. All treatment emergent AEs and SAEs were collected and reported. The same event may appear as both AE and SAE. All-cause mortality data included all anticipated and unanticipated deaths due to any cause. Analysis was done on participants who received at least one dose of study drug.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Phase 1 (Palbociclib + Letrozole)
In Cycle 1 (3 weeks), participants received single agent palbociclib 125 mg/d orally for 2 weeks followed by 1 week off treatment. In Cycles 2 and beyond (4 weeks each), participants received letrozole 2.5 mg/d in a continuous regimen plus Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment.
0
12
2
12
12
12
EG001
Phase 2 (Palbociclib + Letrozole)
All participants who were randomized to letrozole plus palbociclib in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. In Ph2P1 and Ph2P2, the participants received palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and letrozole 2.5 mg/d orally in a continuous regimen.
3
83
22
83
83
83
EG002
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
1
77
6
77
57
77
EG003
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
1
33
10
33
33
33
EG004
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
0
29
2
29
22
29
EG005
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
2
50
12
50
50
50
EG006
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
1
48
4
48
35
48
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG0030 affected33 at risk
EG0040 affected29 at risk
EG0050 affected50 at risk
EG0061 affected48 at risk
Cardiac failure
Cardiac disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Colitis ischaemic
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Gastrointestinal disorder
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Ileus
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Oesophageal achalasia
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Asthenia
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Chest pain
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Disease progression
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Pain
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Erysipelas
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Gangrene
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Influenza
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Staphylococcal bacteraemia
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Fractured sacrum
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Hip fracture
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Intervertebral disc protrusion
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Fallopian tube cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Neuralgia
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Renal disorder
Renal and urinary disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Urethral obstruction
Renal and urinary disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0014 affected83 at risk
EG0020 affected77 at risk
EG003
Subcutaneous emphysema
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Campylobacter infection
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Infective exacerbation of chronic obstructive airways disease
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Mastoiditis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Upper limb fracture
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Osteonecrosis of jaw
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Plasma cell myeloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Brain stem infarction
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0004 affected12 at risk
EG00129 affected83 at risk
EG0023 affected77 at risk
EG00313 affected33 at risk
EG0040 affected29 at risk
EG00516 affected50 at risk
EG0063 affected48 at risk
Leukopenia
Blood and lymphatic system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0008 affected12 at risk
EG00136 affected83 at risk
EG0023 affected77 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0013 affected83 at risk
EG0020 affected77 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG00011 affected12 at risk
EG00162 affected83 at risk
EG0024 affected77 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG00116 affected83 at risk
EG0022 affected77 at risk
EG003
Dry eye
Eye disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0015 affected83 at risk
EG0020 affected77 at risk
EG003
Lacrimation increased
Eye disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0013 affected83 at risk
EG0020 affected77 at risk
EG003
Visual impairment
Eye disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0014 affected83 at risk
EG0021 affected77 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0022 affected77 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0022 affected77 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0017 affected83 at risk
EG0024 affected77 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0024 affected77 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG00113 affected83 at risk
EG0027 affected77 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0006 affected12 at risk
EG00118 affected83 at risk
EG0029 affected77 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0013 affected83 at risk
EG0024 affected77 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG0014 affected83 at risk
EG0022 affected77 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0021 affected77 at risk
EG003
Food poisoning
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0021 affected77 at risk
EG003
Chronic gastritis
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0021 affected77 at risk
EG003
Gingival pain
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0014 affected83 at risk
EG0020 affected77 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0012 affected83 at risk
EG0021 affected77 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0006 affected12 at risk
EG00125 affected83 at risk
EG00211 affected77 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG00110 affected83 at risk
EG0022 affected77 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0016 affected83 at risk
EG0022 affected77 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG00115 affected83 at risk
EG0023 affected77 at risk
EG003
Asthenia
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG00111 affected83 at risk
EG0024 affected77 at risk
EG003
Chest pain
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0013 affected83 at risk
EG0024 affected77 at risk
EG003
Facial pain
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Fatigue
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG00010 affected12 at risk
EG00134 affected83 at risk
EG00218 affected77 at risk
EG003
Influenza like illness
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0015 affected83 at risk
EG0022 affected77 at risk
EG003
Mucosal inflammation
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0017 affected83 at risk
EG0022 affected77 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Oedema peripheral
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0016 affected83 at risk
EG0028 affected77 at risk
EG003
Pain
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0013 affected83 at risk
EG0023 affected77 at risk
EG003
Pyrexia
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0019 affected83 at risk
EG0022 affected77 at risk
EG003
Temperature intolerance
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0011 affected83 at risk
EG0021 affected77 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0013 affected83 at risk
EG0022 affected77 at risk
EG003
Cystitis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0013 affected83 at risk
EG0021 affected77 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0022 affected77 at risk
EG003
Ear infection
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0021 affected77 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0021 affected77 at risk
EG003
Influenza
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0018 affected83 at risk
EG0021 affected77 at risk
EG003
Localised infection
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG00112 affected83 at risk
EG0027 affected77 at risk
EG003
Oral herpes
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0013 affected83 at risk
EG0020 affected77 at risk
EG003
Pneumonia
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0022 affected77 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0012 affected83 at risk
EG0022 affected77 at risk
EG003
Skin infection
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0012 affected83 at risk
EG0021 affected77 at risk
EG003
Tooth infection
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG00112 affected83 at risk
EG0022 affected77 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0019 affected83 at risk
EG0025 affected77 at risk
EG003
Herpes simplex
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0021 affected77 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Thermal burn
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0017 affected83 at risk
EG0023 affected77 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0016 affected83 at risk
EG0021 affected77 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0016 affected83 at risk
EG0021 affected77 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0018 affected83 at risk
EG0023 affected77 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0014 affected83 at risk
EG0025 affected77 at risk
EG003
Blood phosphorus decreased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0014 affected83 at risk
EG0021 affected77 at risk
EG003
Red blood cell count decreased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Weight decreased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0014 affected83 at risk
EG0021 affected77 at risk
EG003
White blood cell count decreased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG00117 affected83 at risk
EG0025 affected77 at risk
EG003
Diabetes mellitus
Metabolism and nutrition disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0014 affected83 at risk
EG0022 affected77 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0012 affected83 at risk
EG0021 affected77 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0013 affected83 at risk
EG0022 affected77 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0005 affected12 at risk
EG00122 affected83 at risk
EG00214 affected77 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG00117 affected83 at risk
EG00213 affected77 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG00110 affected83 at risk
EG0023 affected77 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0015 affected83 at risk
EG0023 affected77 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0013 affected83 at risk
EG0023 affected77 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0019 affected83 at risk
EG0025 affected77 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0016 affected83 at risk
EG0023 affected77 at risk
EG003
Osteonecrosis of jaw
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0013 affected83 at risk
EG0020 affected77 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG0019 affected83 at risk
EG0027 affected77 at risk
EG003
Spinal pain
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0015 affected83 at risk
EG0023 affected77 at risk
EG003
Temporomandibular joint syndrome
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG00110 affected83 at risk
EG0023 affected77 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0016 affected83 at risk
EG0020 affected77 at risk
EG003
Headache
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0004 affected12 at risk
EG00112 affected83 at risk
EG0028 affected77 at risk
EG003
Memory impairment
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0012 affected83 at risk
EG0021 affected77 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0019 affected83 at risk
EG0024 affected77 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0022 affected77 at risk
EG003
Sciatica
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Sinus headache
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Syncope
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0012 affected83 at risk
EG0024 affected77 at risk
EG003
Depression
Psychiatric disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG0014 affected83 at risk
EG0025 affected77 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG0018 affected83 at risk
EG0026 affected77 at risk
EG003
Mood altered
Psychiatric disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0014 affected83 at risk
EG0021 affected77 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0013 affected83 at risk
EG0021 affected77 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG0014 affected83 at risk
EG0022 affected77 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0014 affected83 at risk
EG0021 affected77 at risk
EG003
Breast discomfort
Reproductive system and breast disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Breast pain
Reproductive system and breast disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0024 affected77 at risk
EG003
Pelvic pain
Reproductive system and breast disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0012 affected83 at risk
EG0022 affected77 at risk
EG003
Vaginal discharge
Reproductive system and breast disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Vulvovaginal pruritus
Reproductive system and breast disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG00112 affected83 at risk
EG0028 affected77 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0005 affected12 at risk
EG00114 affected83 at risk
EG0027 affected77 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0019 affected83 at risk
EG0021 affected77 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0019 affected83 at risk
EG0021 affected77 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0021 affected77 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Snoring
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG00118 affected83 at risk
EG0022 affected77 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0016 affected83 at risk
EG0024 affected77 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0014 affected83 at risk
EG0021 affected77 at risk
EG003
Ingrown hair
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Nail disorder
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0015 affected83 at risk
EG0021 affected77 at risk
EG003
Pain of skin
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0015 affected83 at risk
EG0022 affected77 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG0017 affected83 at risk
EG0024 affected77 at risk
EG003
Skin disorder
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Skin swelling
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Swelling face
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Haematoma
Vascular disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 events0 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Hot flush
Vascular disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0003 affected12 at risk
EG00119 affected83 at risk
EG00211 affected77 at risk
EG003
Hypertension
Vascular disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0016 affected83 at risk
EG0025 affected77 at risk
EG003
Lymphoedema
Vascular disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0014 affected83 at risk
EG0020 affected77 at risk
EG003
Peripheral vascular disorder
Vascular disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Phlebitis
Vascular disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Tumour pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0022 affected77 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Thyroid mass
Endocrine disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Cataract
Eye disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Presbyopia
Eye disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Oral disorder
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Chills
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Face oedema
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Peripheral swelling
General disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0014 affected83 at risk
EG0022 affected77 at risk
EG003
Gingivitis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0002 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Periorbital haemorrhage
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Skin injury
Injury, poisoning and procedural complications
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0020 affected77 at risk
EG003
Arthropathy
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0011 affected83 at risk
EG0021 affected77 at risk
EG003
Radicular pain
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Incontinence
Renal and urinary disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0021 affected77 at risk
EG003
Lower respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0010 affected83 at risk
EG0020 affected77 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0001 affected12 at risk
EG0013 affected83 at risk
EG0021 affected77 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0011 affected83 at risk
EG0024 affected77 at risk
EG003
Cellulitis
Infections and infestations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0022 affected77 at risk
EG003
Weight increased
Investigations
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0013 affected83 at risk
EG0026 affected77 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0020 affected77 at risk
EG003
Limb discomfort
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0010 affected83 at risk
EG0022 affected77 at risk
EG003
Osteoporosis
Musculoskeletal and connective tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0012 affected83 at risk
EG0021 affected77 at risk
EG003
Peripheral sensory neuropathy
Nervous system disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0013 affected83 at risk
EG0020 affected77 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA (v20.1)
Non-systematic Assessment
EG0000 affected12 at risk
EG0013 affected83 at risk
EG0023 affected77 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Point of Contact
Title
Organization
Phone
Extension
Email
Pfizer ClinicalTrials.gov Call Center
Pfizer, Inc.
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com
ID
Term
D001943
Breast Neoplasms
Ancestor Terms
ID
Term
D009371
Neoplasms by Site
D009369
Neoplasms
D001941
Breast Diseases
D012871
Skin Diseases
D017437
Skin and Connective Tissue Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C500026
palbociclib
D000077289
Letrozole
Ancestor Terms
ID
Term
D009570
Nitriles
D009930
Organic Chemicals
D014230
Triazoles
D001393
Azoles
D006573
Heterocyclic Compounds, 1-Ring
D006571
Heterocyclic Compounds
Browse Leaves
Not provided
Browse Branches
Not provided
0
18-44 Years
Title
Measurements
BG0001
BG0012
BG0024
BG0037
45-64 Years
Title
Measurements
BG0006
BG00145
BG00238
BG00389
>= 65 Years
Title
Measurements
BG0005
BG00137
BG00239
BG00381
81
BG003177
Male
BG0000
BG0010
BG0020
BG0030
0
BG0030
Asian
BG0000
BG0016
BG0024
BG00310
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
Black or African American
BG0000
BG0011
BG0021
BG0032
White
BG00011
BG00176
BG00272
BG003159
More than one race
BG0000
BG0010
BG0020
BG0030
Unknown or Not Reported
BG0001
BG0011
BG0024
BG0036
Title
Measurements
OG00011
Participants with Grade 5 AEs
Title
Measurements
OG0000
12
Title
Denominators
Categories
Participants with AEs
Title
Measurements
OG00012
Participants with SAEs
Title
Measurements
OG0000
Participants with Grade 3 or 4 AEs
Title
Measurements
OG00011
Participants with Grade 5 AEs
Title
Measurements
OG0000
Units
Counts
Participants
OG00012
Title
Denominators
Categories
Grade 4 Neutropenia
Title
Measurements
OG0002
<80% of doses due to elevated creatinine
Title
Measurements
OG0001
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00084
OG00181
OG00234
OG00332
OG00450
OG00549
Title
Denominators
Categories
Title
Measurements
OG00020.2(13.8 to 27.5)
OG00110.2(5.7 to 12.6)
OG00226.1(11.2 to NA)Not reached
OG0035.7(2.6 to 10.5)
OG00418.1(13.1 to 27.5)
OG00511.1(7.1 to 16.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
The primary hypothesis to be tested was H0: λ=1 versus. HA: λ<1, where λ was the palbociclib plus letrozole:letrozole alone hazard ratio (HR). A HR less than 1 indicates a reduction in hazard rate in favor of Palbociclib + Letrozole. Stratified analysis was presented above.
Log Rank
0.0004
1-sided p-value from the log-rank test stratified by stratification factors per randomization and Part.
Hazard Ratio (HR)
0.488
2-Sided
95
0.319
0.748
Superiority or Other (legacy)
OG002
OG003
The primary hypothesis to be tested was H0: λ=1 versus. HA: λ<1, where λ was the palbociclib plus letrozole:letrozole alone hazard ratio (HR). A HR less than 1 indicates a reduction in hazard rate in favor of Palbociclib + Letrozole. Unstratified analysis was presented above.
Log Rank
<0.0001
1-sided p-value from the log-rank test.
Hazard Ratio (HR)
0.299
2-Sided
95
0.156
0.572
Superiority or Other (legacy)
OG004
OG005
The primary hypothesis to be tested was H0: λ=1 versus. HA: λ<1, where λ was the palbociclib plus letrozole:letrozole alone hazard ratio (HR). A HR less than 1 indicates a reduction in hazard rate in favor of Palbociclib + Letrozole. Unstratified analysis was presented above.
Log Rank
0.0046
1-sided p-value from the log-rank test.
Hazard Ratio (HR)
0.508
2-Sided
95
0.303
0.853
Superiority or Other (legacy)
Participants
OG00012
Title
Denominators
Categories
Title
Measurements
OG00033.3(9.9 to 65.1)
12
Title
Denominators
Categories
Title
Measurements
OG00083.3(51.6 to 97.9)
Units
Counts
Participants
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG0001982± 29
OG0011933± 31
Units
Counts
Participants
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG000115.8± 28
OG001108.4± 29
Units
Counts
Participants
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG0007.92± 28(2.17 to 8.20)
OG0017.92± 29(2.00 to 8.08)
Units
Counts
Participants
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG00028.81± 5.0462(2.17 to 8.20)
OG001NA± NA(2.00 to 8.08)Not calculated
Units
Counts
Participants
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG00063.08± 29(2.17 to 8.20)
OG001NA± NA(2.00 to 8.08)Not calculated
Units
Counts
Participants
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG0002583± 26(2.17 to 8.20)
OG001NA± NA(2.00 to 8.08)Not calculated
Participants
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG0001739± 30(2.17 to 8.20)
OG0011936± 35(2.00 to 8.08)
Participants
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG00094.95± 27(2.17 to 8.20)
OG001104.0± 31(2.00 to 8.08)
OG00012
OG00112
Title
Denominators
Categories
Title
Measurements
OG0002.00± 27(0.833 to 4.13)
OG0011.04± 31(0.00 to 4.42)
Units
Counts
Participants
OG00012
Title
Denominators
Categories
QTcB - Change <30
Title
Measurements
OG0009
QTcB - 30 ≤ change <60
Title
Measurements
OG0003
QTcB - Change ≥60
Title
Measurements
OG0000
QTcF - Change <30
Title
Measurements
OG00011
QTcF - 30 ≤ change <60
Title
Measurements
OG0001
QTcF - Change ≥60
Title
Measurements
OG0000
QTcS - Change <30
Title
Measurements
OG0008
QTcS - 30 ≤ change <60
Title
Measurements
OG0004
QTcS - Change ≥60
Title
Measurements
OG0000
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00084
OG00181
OG00234
OG00332
OG00450
OG00549
Title
Denominators
Categories
Title
Measurements
OG00037.5(31.4 to 47.8)
OG00134.5(27.4 to 42.6)
OG00237.5(27.6 to 58.8)
OG00333.3(26.0 to 54.3)
OG00435.1(28.1 to 47.8)
OG00535.7(26.6 to 46.7)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Stratified analysis was presented above. Hazard ratio was assuming proportional hazards, a hazard ratio less than 1 indicated a reduction in hazard rate in favor of palbociclib + letrozole.
Log Rank
0.2812
1-sided p-value from the log-rank test stratified by Part (α = 0.10).
Hazard Ratio (HR)
0.897
2-Sided
95
0.623
1.294
Superiority or Other (legacy)
OG002
OG003
Unstratified analysis was presented above.
Log Rank
0.2803
1-sided p-value from the unstratified log-rank test (α=0.10).
Hazard Ratio (HR)
0.837
2-Sided
95
0.458
1.527
Superiority or Other (legacy)
OG004
OG005
Unstratified analysis was presented above.
Log Rank
0.3875
1-sided p-value from the unstratified log-rank test (α=0.10).
Hazard Ratio (HR)
0.935
2-Sided
95
0.590
1.480
Superiority or Other (legacy)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00084
OG00181
OG00234
OG00332
OG00450
OG00549
Title
Denominators
Categories
Title
Measurements
OG00042.9(32.1 to 54.1)
OG00133.3(23.2 to 44.7)
OG00244.1(27.2 to 62.1)
OG00325.0(11.5 to 43.4)
OG00442.0(28.2 to 56.8)
OG00538.8(25.2 to 53.8)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Objective Response CI was calculated using the exact Clopper-Pearson method. The stratified analysis presented above was based on CMH test stratified by Part. An Odds Ratio >1 means better response in favor of palbociclib + letrozole arm.
Cochran-Mantel-Haenszel
0.1347
1-sided p-value is from the stratified exact test (1-sided, α =0.10)
Odds Ratio (OR)
1.50
2-Sided
95
0.76
2.97
Superiority or Other (legacy)
OG002
OG003
Unstratified analysis was presented above. Exact CI was based on Clopper-Pearson method.
Chi-squared
0.0849
Chi-square test was used (1-sided, α=0.10)
Odds Ratio (OR)
2.37
2-Sided
95
0.74
7.84
Superiority or Other (legacy)
OG004
OG005
Unstratified analysis was presented above. Exact CI was based on Clopper-Pearson method.
Chi-squared
0.4515
Chi-square test was used (1-sided, α=0.10)
Odds Ratio (OR)
1.14
2-Sided
95
0.48
2.76
Superiority or Other (legacy)
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00065
OG00166
OG00227
OG00323
OG00421
OG00543
Title
Denominators
Categories
Title
Measurements
OG00055.4(42.5 to 67.7)
OG00139.4(27.6 to 52.2)
OG00255.6(35.3 to 74.5)
OG00334.8(16.4 to 57.3)
OG00455.3(38.3 to 71.4)
OG00541.9(27.0 to 57.9)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Objective Response CI was calculated using the exact Clopper-Pearson method. The stratified analysis presented above was based on CMH test stratified by Part. An Odds Ratio >1 means better response in favor of palbociclib + letrozole arm.
Cochran-Mantel-Haenszel
0.0471
1-sided p-value is from the stratified exact test (1-sided, α =0.10)
Odds Ratio (OR)
1.93
2-Sided
95
0.91
4.08
Superiority or Other (legacy)
OG002
OG003
Unstratified analysis was presented above. Exact CI was based on Clopper-Pearson method.
Chi-squared
0.1180
Chi-square test was used (1-sided, α=0.10)
Odds Ratio (OR)
2.34
2-Sided
95
0.65
8.66
Superiority or Other (legacy)
OG004
OG005
Unstratified analysis was presented above. Exact CI was based on Clopper-Pearson method.
Chi-squared
0.1631
Chi-square test was used (1-sided, α=0.10)
Odds Ratio (OR)
1.72
2-Sided
95
0.65
4.54
Superiority or Other (legacy)
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00036
OG00127
OG00215
OG0038
OG00421
OG00519
Title
Denominators
Categories
Title
Measurements
OG00020.3(13.4 to 25.8)
OG00111.1(9.3 to 31.6)
OG00220.9(6.2 to 25.8)
OG00310.8(3.7 to 31.6)
OG00420.2(13.0 to NA)Not reached
OG00514.8(7.4 to NA)Not reached
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00084
OG00181
OG00234
OG00332
OG00450
OG00549
Title
Denominators
Categories
Title
Measurements
OG00081.0(70.9 to 88.7)
OG00158.0(46.5 to 68.9)
OG00276.5(58.8 to 89.3)
OG00343.8(26.4 to 62.3)
OG00484.0(70.9 to 92.8)
OG00567.3(52.5 to 80.1)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
CBR CI was calculated using the exact Clopper-Pearson method. The stratified analysis presented above was based on CMH test stratified by Part. An Odds Ratio >1 means better response in favor of palbociclib + letrozole arm.
Cochran-Mantel-Haenszel
0.0009
1-sided p-value is from the stratified exact test (1-sided, α =0.10).
Odds Ratio (OR)
3.18
2-Sided
95
1.48
6.98
Superiority or Other (legacy)
OG002
OG003
Unstratified analysis was presented above. Exact CI was based on Clopper-Pearson method.
Chi-squared
0.0065
Chi-square test was used (1-sided, α=0.10)
Odds Ratio (OR)
4.18
2-Sided
95
1.30
13.90
Superiority or Other (legacy)
OG004
OG005
Unstratified analysis was presented above. Exact CI was based on Clopper-Pearson method.
Chi-squared
0.0442
Chi-square test was used (1-sided, α=0.10)
Odds Ratio (OR)
2.55
2-Sided
95
0.89
7.70
Superiority or Other (legacy)
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00084
OG00181
OG00234
OG00332
OG00450
OG00549
Title
Denominators
Categories
Title
Measurements
OG00020.2(13.8 to 27.5)
OG00110.2(5.7 to 12.6)
OG00226.1(11.2 to NA)Not reached
OG0035.7(2.6 to 10.5)
OG00418.8(13.1 to 27.5)
OG00511.1(7.1 to 16.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Kaplan-Meier method was applied for median and 95% CI. Hazard ratio was based on assuming proportional hazards, a hazard ratio less than 1 indicates a reduction in hazard rate in favor of palbociclib + letrozole.
Log Rank
<0.0001
1-sided p-value is from the stratified log-rank test (α =0.10).
Hazard Ratio (HR)
0.399
2-Sided
95
0.265
0.601
Superiority or Other (legacy)
OG002
OG003
Unstratified analysis was presented above. Kaplan-Meier method was applied for median and 95% CI.
Log Rank
<0.0001
1-sided p-value is from unstratified log-rank test (α=0.10).
Hazard Ratio (HR)
0.299
2-Sided
95
0.156
0.572
Superiority or Other (legacy)
OG004
OG005
Unstratified analysis was presented above. Kaplan-Meier method was applied for median and 95% CI.
Log Rank
0.0030
1-sided p-value is from unstratified log-rank test (α=0.10).
Hazard Ratio (HR)
0.486
2-Sided
95
0.288
0.822
Superiority or Other (legacy)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00076
OG00174
OG00229
OG00327
OG00447
OG00547
Title
Denominators
Categories
Pain at its worst in the last 24 hours
Title
Measurements
OG0000.6± 0.42(28.4 to NA)
OG0010.1± 0.42(26.4 to NA)
OG0020.2± 0.60(27.6 to NA)
OG0030.0± 0.89(26.0 to NA)
OG0041.2± 0.55(26.0 to NA)
OG0050.1± 0.43(23.4 to NA)
Pain at its least in the last 24 hours
Title
Measurements
OG0000.4± 0.27
OG0010.4± 0.27
OG0020.3± 0.31
OG003
Pain on the average
Title
Measurements
OG0000.2± 0.33
OG0010.2± 0.34
OG002-0.1± 0.48
OG003
Pain right now
Title
Measurements
OG0000.3± 0.35
OG0010.1± 0.36
OG0020.1± 0.31
OG003
Pain Severity Scale
Title
Measurements
OG0000.4± 0.29
OG0010.2± 0.32
OG0020.0± 0.36
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Statistical analysis presented above is for Pain Severity Scale.
t-test, 2 sided
0.6900
P-values are based on 2-sample t-test.
Mean Difference (Final Values)
0.2
2-Sided
95
-0.7
1.0
Superiority or Other (legacy)
OG002
OG003
Statistical analysis presented above is for Pain Severity Scale.
t-test, 2 sided
0.7125
P-values are based on 2-sample t-test.
Mean Difference (Final Values)
-0.3
2-Sided
95
-1.8
1.2
Superiority or Other (legacy)
OG004
OG005
Statistical analysis presented above is for Pain Severity Scale.
t-test, 2 sided
0.4012
P-values are based on 2-sample t-test.
Mean Difference (Final Values)
0.5
2-Sided
95
-0.6
1.5
Superiority or Other (legacy)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00076
OG00174
OG00229
OG00327
OG00447
OG00547
Title
Denominators
Categories
General Activity
Title
Measurements
OG0001.1± 0.40(28.4 to NA)
OG0010.2± 0.31(26.4 to NA)
OG0021.0± 0.66(27.6 to NA)
OG0030.2± 0.58(26.0 to NA)
OG0041.2± 0.51(26.0 to NA)
OG0050.3± 0.37(23.4 to NA)
Mood
Title
Measurements
OG0000.8± 0.50
OG0010.2± 0.36
OG0020.6± 0.72
OG003
Walking ability
Title
Measurements
OG0000.8± 0.46
OG0010.1± 0.35
OG0021.0± 0.55
OG003
Normal work
Title
Measurements
OG0000.7± 0.48
OG0010.3± 0.39
OG0021.0± 0.53
OG003
Relations
Title
Measurements
OG0000.8± 0.32
OG0010.8± 0.32
OG0020.6± 0.34
OG003
Sleep
Title
Measurements
OG0000.6± 0.43
OG0010.3± 0.35
OG0020.1± 0.53
OG003
Enjoyment of life
Title
Measurements
OG0000.8± 0.46
OG0010.6± 0.41
OG0020.4± 0.34
OG003
Pain Interference Scale
Title
Measurements
OG0000.8± 0.34
OG0010.4± 0.30
OG0020.7± 0.42
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Statistical analysis presented above is for Pain Interference Scale.
t-test, 2 sided
0.3346
P-values are based on 2-sample t-test.
Mean Difference (Final Values)
0.4
2-Sided
95
-0.5
1.3
Superiority or Other (legacy)
OG002
OG003
Statistical analysis presented above is for Pain Interference Scale.
t-test, 2 sided
0.5630
P-values are based on 2-sample t-test.
Mean Difference (Final Values)
0.4
2-Sided
95
-1.0
1.9
Superiority or Other (legacy)
OG004
OG005
Statistical analysis presented above is for Pain Severity Scale.
t-test, 2 sided
0.4427
P-values are based on 2-sample t-test.
Mean Difference (Final Values)
0.5
2-Sided
95
-0.7
1.6
Superiority or Other (legacy)
OG003
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00022
OG00124
OG00250
OG00348
Title
Denominators
Categories
CCND1>=1.5
Title
Measurements
OG00012± 0.66(27.6 to NA)
OG0019± 0.58(26.0 to NA)
OG00239± 0.51(26.0 to NA)
OG00344± 0.37(23.4 to NA)
p16/INK4A<0.8
Title
Measurements
OG0000± 0.72
OG0012± 0.62
OG00219± 0.69
OG003
CCND1>=1.5 and p16/INK4A<0.8
Title
Measurements
OG0000± 0.55
OG0012± 0.63
OG0028± 0.67
OG003
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00074
OG00171
OG00224
OG00326
OG00450
OG00545
Title
Denominators
Categories
<=20%
Title
Measurements
OG00026± 0.40(28.4 to NA)
OG00131± 0.31(26.4 to NA)
OG0027± 0.66(27.6 to NA)
OG00316± 0.58(26.0 to NA)
OG00419± 0.51(26.0 to NA)
OG00515± 0.37(23.4 to NA)
>20%
Title
Measurements
OG00048± 0.50
OG00140± 0.36
OG00217± 0.72
OG003
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00045
OG00135
OG00212
OG00316
OG00433
OG00519
Title
Denominators
Categories
CyclinD1 - Positive
Title
Measurements
OG00041± 0.40(28.4 to NA)
OG00132± 0.31(26.4 to NA)
OG00210± 0.66(27.6 to NA)
OG00316± 0.58(26.0 to NA)
OG00431± 0.51(26.0 to NA)
OG00516± 0.37(23.4 to NA)
CyclinD1 - Negative
Title
Measurements
OG0003± 0.50
OG0013± 0.36
OG0022± 0.72
OG003
RB - Positive
Title
Measurements
OG00041
OG00132
OG00210
OG003
RB - Negative
Title
Measurements
OG0002
OG0012
OG0022
OG003
OG00072
OG00172
Title
Denominators
Categories
CCND1
Title
Measurements
OG0002.76± 1.875(28.4 to NA)
OG0012.73± 1.559(26.4 to NA)
p16/INK4A
Title
Measurements
OG0000.83± 0.224
OG0010.87± 0.173
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00076
OG00174
OG00230
OG00328
OG00446
OG00546
Title
Denominators
Categories
CYP19A1 - A/A Genotype
Title
Measurements
OG0007.9± 0.42(28.4 to NA)
OG0015.4± 0.42(26.4 to NA)
OG00210.0± 0.60(27.6 to NA)
OG00310.7± 0.89(26.0 to NA)
OG0046.5± 0.55(26.0 to NA)
OG0052.2± 0.43(23.4 to NA)
CYP19A1 - C/A Genotype
Title
Measurements
OG00034.2± 0.27
OG00136.5± 0.27
OG00233.3± 0.31
OG003
CYP19A1 - C/C Genotype
Title
Measurements
OG00057.9± 0.33
OG00158.1± 0.34
OG00256.7± 0.48
OG003
CCND1 - A/A Genotype
Title
Measurements
OG00026.3± 0.35
OG00128.4± 0.36
OG00233.3± 0.31
OG003
CCND1 - G/A Genotype
Title
Measurements
OG00047.4± 0.29
OG00147.3± 0.32
OG00243.3± 0.36
OG003
CCND1 - G/G Genotype
Title
Measurements
OG00026.3
OG00124.3
OG00223.3
OG003
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
Units
Counts
Participants
OG00083
OG00177
OG00233
OG00329
OG00450
OG00548
Title
Denominators
Categories
Participants with AEs
Title
Measurements
OG00083
OG00166
OG00233
OG00325
OG00450
OG00541
Participants with SAEs
Title
Measurements
OG00022
OG0016
OG00210
OG003
Participants with Grade 3 or 4 AEs
Title
Measurements
OG00070
OG00119
OG00229
OG003
Participants with Grade 5 AEs
Title
Measurements
OG0001
OG0010
OG0020
OG003
OG001
Phase 2 (Letrozole)
All participants who were randomized to receive letrozole alone in both Phase 2 part 1 (Ph2P1) and Phase 2 part 2 (Ph2P2) are combined and presented. This was considered as control arm. Letrozole 2.5 mg/d was administered orally in a continuous regimen.
OG002
Ph2P1 (Palbociclib + Letrozole)
All participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG003
Ph2P1 (Letrozole)
Participants were randomized to receive Letrozole alone. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.
OG004
Ph2P2 (Palbociclib + Letrozole)
Participants were randomized to receive Letrozole plus Palbociclib. Palbociclib 125 mg/d orally for 3 weeks followed by 1 week off treatment and Letrozole 2.5 mg/d orally in a continuous regimen.
OG005
Ph2P2 (Letrozole)
Participants were randomized to receive Letrozole. Letrozole 2.5 mg/d was administered orally in a continuous regimen. This was considered as control arm.