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This Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial in China will evaluate the efficacy and safety of pertuzumab + trastuzumab + docetaxel compared with placebo + trastuzumab + docetaxel in participants with previously untreated HER2-positive metastatic breast cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | Active Comparator | Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| Arm B: Pertuzumab + Trastuzumab + Docetaxel | Experimental | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Docetaxel | Drug | Docetaxel (75-mg/m^2) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeters (mm), and the appearance of new lesions. The Kaplan-Meier approach was used to estimate median PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline, at randomization plus 1 day). | From date of randomization until date of PFS event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks; Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks) |
| Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Progression-Free Survival at 1 to 3 Years, as Determined by the Investigator Using RECIST v1.1 | Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for PFS at 1, 2, and 3 years. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline visit, at randomization plus 1 day). At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks. | At 1, 2, and 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate median OS for each treatment arm. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. The results reported here are from the final analysis. At the primary completion date, the median duration of OS had not been reached and OS data was not considered mature due to the few number of events reported. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHINESE ACADEMY OF MEDICAL SCIENCE; CANCER INST. & HOSPITAL; Medical ward | Beijing | 100021 | China | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32564260 | Derived | Xu B, Li W, Zhang Q, Shao Z, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhang H, Lei G, Restuccia E. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2020 Aug;182(3):689-697. doi: 10.1007/s10549-020-05728-w. Epub 2020 Jun 20. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Placebo + Trastuzumab + Docetaxel | Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity. Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 7, 2020 | Nov 15, 2021 |
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| Pertuzumab | Drug | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| Placebo | Drug | Placebo matched to pertuzumab was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| Trastuzumab | Drug | Trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| From date of randomization until the date of death from any cause (Median [range] time on study for Arm A vs. Arm B at Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks) |
| Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival at 1 to 3 Years | Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS (i.e., alive) at 1, 2, and 3 years. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks. | At 1, 2, and 3 Years |
| Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1 | An objective response was defined as a complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. Also per RECIST v1.1, stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study; PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The same assessment technique must be used throughout the study for evaluating a particular lesion, and the same investigator should assess all tumor responses for each participant. Participants without a post-baseline tumor assessment were considered non-responders. | At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks) |
| Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1 | Duration of objective response was defined as the time from the first occurrence of a documented objective response (complete response [CR] or partial response [PR]) to the time of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. The Kaplan-Meier approach was used to estimate median duration of objective response. Data for participants who did not have an event were censored at the time of the last tumor assessment (if no tumor assessments were performed after baseline visit, at randomization plus 1 day). | From date of first occurrence of documented objective response to date of event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks) |
| Number of Participants With at Least One Adverse Event | The number of participants per treatment arm experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. Adverse events reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
| Number of Participants With at Least One Grade ≥3 Adverse Event | Adverse event (AE) severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0); if the AE was not specifically listed, the following grades of severity were used: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening or disabling; and Grade 5 = death. Severe and serious are not synonymous. Severity refers to the intensity of an AE, whereas a serious AE must meet criteria set out in the protocol; both were independently assessed for each AE. AEs reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
| Number of Participants With at Least One Adverse Event Leading to Withdrawal From Any Treatment | Adverse events reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
| Number of Participants With Symptomatic Left Ventricular Systolic Dysfunction (LVSD), as Determined Using Echocardiography (ECHO) or Multiple-Gated Acquisition (MUGA) Scan | The number of participants with symptomatic left ventricular systolic dysfunction (LVSD) at any time during the study, as determined using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan, were summarized by treatment arm. Symptomatic LVSD was evaluated according to NCI CTCAE v4.0 (for "heart failure") and the New York Heart Association (NYHA) classification. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
| Number of Participants With an Asymptomatic Decline in Left Ventricular Ejection Fraction (LVEF) Event, as Determined Using ECHO or MUGA Scan | An asymptomatic decline in LVEF event is reported as an adverse event of "ejection fraction decreased" and is defined as either of the following: an absolute decrease in LVEF of ≥10 percentage points from baseline to an LVEF of <50%; or an asymptomatic decrease in LVEF requiring treatment or leading to discontinuation of pertuzumab (or placebo) and trastuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
| Number of Participants by the LVEF Abnormality Status Categories Over Time, as Determined by the Change From Baseline in LVEF Using ECHO or MUGA Scans | Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method was to be used throughout the study, to the extent possible. The LVEF abnormality status categories, as a change relative to LVEF at baseline, included: Increase or no change in LVEF; Decrease of <10 LVEF points; Absolute LVEF value ≥50% and a decrease of ≥10 LVEF points; and Absolute LVEF value <50% and a decrease of ≥10 LVEF points. The overall worst LVEF value was defined as the lowest post-baseline value up to the end of the study, including unscheduled assessments and the post-treatment period. | Baseline, Weeks 9, 18, 27, 36, 45, 54, 63, 72, 81, 90, 99, 108, 117, 126, 135, 144, 153, 162, 171, 180, 189, 198, 207, 216, and 225, Study Drug Discontinuation Visit (up to 4 years, 4 months), and Treatment-Free Follow-Up at 6 months, and 1 and 2 years |
| Baseline LVEF and Change From Baseline to Maximum On-Treatment Decrease in LVEF at Any Point During the Study | The baseline left ventricular ejection fraction (LVEF) and change from baseline to the maximum on-treatment decrease in LVEF at any point during the study are reported here. LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method should have been used throughout the study, to the extent possible. At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks. | Baseline and every 9 weeks from date of randomization until treatment discontinuation (up to 4 years, 4 months) |
| Beijing Cancer Hospital |
| Beijing |
| 100142 |
| China |
| Chinese PLA General Hospital | Beijing | 100853 | China |
| the First Hospital of Jilin University | Changchun | 130021 | China |
| Changzhou First People's Hospital | Changzhou | 213003 | China |
| West China Hospital, Sichuan University | Chengdu | 610041 | China |
| The 900th Hospital of PLA joint service support force | Fuzhou | 110016 | China |
| Guangdong General Hospital | Guangzhou | 510080 | China |
| Harbin Medical University Cancer Hospital | Harbin | 150081 | China |
| Jiangsu province hospital; surgery on galactophore | Nanjing | 210029 | China |
| Jiangsu Cancer Hospital | Nanjing | 211100 | China |
| Fudan University Shanghai Cancer Center | Shanghai | 200120 | China |
| First Hospital of China Medical University | Shenyang | 110001 | China |
| Liaoning cancer Hospital & Institute | Shenyang | 110042 | China |
| Zhejiang Cancer Hospital | Zhejiang | 310022 | China |
| FG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| Received Any Study Treatment | Safety Population |
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| Crossed Over From Placebo to Receive Pertuzumab |
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| COMPLETED |
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| NOT COMPLETED |
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Intent-to-Treat (ITT) population: consists of all randomized participants, regardless of whether they received any study treatment. Participants are grouped according to the treatment group to which they were randomized.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Placebo + Trastuzumab + Docetaxel | Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity. Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. |
| BG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Disease Type: Visceral or Non-Visceral Disease | Count of Participants | Participants |
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| Hormone Receptor Status | Count of Participants | Participants |
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| Measurable or Non-Measurable Disease, According to RECIST v1.1 | Count of Participants | Participants |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeters (mm), and the appearance of new lesions. The Kaplan-Meier approach was used to estimate median PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline, at randomization plus 1 day). | Intent-to-Treat (ITT) population: consists of all randomized participants, regardless of whether they received any study treatment. Participants are grouped according to the treatment group to which they were randomized. | Posted | Median | 95% Confidence Interval | months | From date of randomization until date of PFS event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks; Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks) |
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| Primary | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Progression-Free Survival at 1 to 3 Years, as Determined by the Investigator Using RECIST v1.1 | Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for PFS at 1, 2, and 3 years. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline visit, at randomization plus 1 day). At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks. | ITT population: consists of all randomized participants, regardless of whether they received any study treatment. Participants are grouped according to the treatment group to which they were randomized. The number analyzed per timepoint represents the number of participants remaining at risk for a PFS event at that timepoint. | Posted | Number | 95% Confidence Interval | estimate of percentage of participants | At 1, 2, and 3 years |
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| Secondary | Overall Survival | Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate median OS for each treatment arm. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. The results reported here are from the final analysis. At the primary completion date, the median duration of OS had not been reached and OS data was not considered mature due to the few number of events reported. | ITT population: consists of all randomized participants, regardless of whether they received any study treatment. Participants are grouped according to the treatment group to which they were randomized. | Posted | Median | Inter-Quartile Range | months | From date of randomization until the date of death from any cause (Median [range] time on study for Arm A vs. Arm B at Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks) |
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| Secondary | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival at 1 to 3 Years | Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS (i.e., alive) at 1, 2, and 3 years. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks. | ITT population: consists of all randomized participants, regardless of whether they received any study treatment. Participants are grouped according to the treatment group to which they were randomized. The number analyzed per timepoint represents the number of participants remaining at risk for an OS event at that timepoint. | Posted | Number | 95% Confidence Interval | estimate of percentage of participants | At 1, 2, and 3 Years |
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| Secondary | Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1 | An objective response was defined as a complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. Also per RECIST v1.1, stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study; PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The same assessment technique must be used throughout the study for evaluating a particular lesion, and the same investigator should assess all tumor responses for each participant. Participants without a post-baseline tumor assessment were considered non-responders. | ITT population: consists of all randomized participants, regardless of whether they received any study treatment. Participants are grouped according to the treatment group to which they were randomized. Only participants with measurable disease at baseline were included in the analysis. | Posted | Number | 95% Confidence Interval | percentage of participants | At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks) |
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| Secondary | Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1 | Duration of objective response was defined as the time from the first occurrence of a documented objective response (complete response [CR] or partial response [PR]) to the time of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. The Kaplan-Meier approach was used to estimate median duration of objective response. Data for participants who did not have an event were censored at the time of the last tumor assessment (if no tumor assessments were performed after baseline visit, at randomization plus 1 day). | ITT population: consists of all randomized participants, regardless of whether they received any study treatment. Participants are grouped according to the treatment group to which they were randomized. Only participants with measurable disease at baseline who achieved an objective response during the study were included in the analysis. | Posted | Median | 95% Confidence Interval | months | From date of first occurrence of documented objective response to date of event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks) |
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| Secondary | Number of Participants With at Least One Adverse Event | The number of participants per treatment arm experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. Adverse events reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | Safety population, which includes participants who received at least one dose of any study drug, with participants grouped according to the treatment received. Following approval of Protocol version 4 (07-March-2020), 12 Arm A participants who were receiving placebo crossed over to receive open-label treatment with pertuzumab. | Posted | Count of Participants | Participants | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
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| Secondary | Number of Participants With at Least One Grade ≥3 Adverse Event | Adverse event (AE) severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0); if the AE was not specifically listed, the following grades of severity were used: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening or disabling; and Grade 5 = death. Severe and serious are not synonymous. Severity refers to the intensity of an AE, whereas a serious AE must meet criteria set out in the protocol; both were independently assessed for each AE. AEs reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | Safety population, which includes participants who received at least one dose of any study drug, with participants grouped according to the treatment received. Following approval of Protocol version 4 (07-March-2020), 12 Arm A participants who were receiving placebo crossed over to receive open-label treatment with pertuzumab. | Posted | Count of Participants | Participants | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
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| Secondary | Number of Participants With at Least One Adverse Event Leading to Withdrawal From Any Treatment | Adverse events reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | Safety population, which includes participants who received at least one dose of any study drug, with participants grouped according to the treatment received. Following approval of Protocol version 4 (07-March-2020), 12 Arm A participants who were receiving placebo crossed over to receive open-label treatment with pertuzumab. | Posted | Count of Participants | Participants | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
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| Secondary | Number of Participants With Symptomatic Left Ventricular Systolic Dysfunction (LVSD), as Determined Using Echocardiography (ECHO) or Multiple-Gated Acquisition (MUGA) Scan | The number of participants with symptomatic left ventricular systolic dysfunction (LVSD) at any time during the study, as determined using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan, were summarized by treatment arm. Symptomatic LVSD was evaluated according to NCI CTCAE v4.0 (for "heart failure") and the New York Heart Association (NYHA) classification. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | Safety population, which includes participants who received at least one dose of any study drug, with participants grouped according to the treatment received. Following approval of Protocol version 4 (07-March-2020), 12 Arm A participants who were receiving placebo crossed over to receive open-label treatment with pertuzumab. | Posted | Count of Participants | Participants | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With an Asymptomatic Decline in Left Ventricular Ejection Fraction (LVEF) Event, as Determined Using ECHO or MUGA Scan | An asymptomatic decline in LVEF event is reported as an adverse event of "ejection fraction decreased" and is defined as either of the following: an absolute decrease in LVEF of ≥10 percentage points from baseline to an LVEF of <50%; or an asymptomatic decrease in LVEF requiring treatment or leading to discontinuation of pertuzumab (or placebo) and trastuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. | Safety population, which includes participants who received at least one dose of any study drug, with participants grouped according to the treatment received. Following approval of Protocol version 4 (07-March-2020), 12 Arm A participants who were receiving placebo crossed over to receive open-label treatment with pertuzumab. | Posted | Count of Participants | Participants | From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months) |
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| Secondary | Number of Participants by the LVEF Abnormality Status Categories Over Time, as Determined by the Change From Baseline in LVEF Using ECHO or MUGA Scans | Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method was to be used throughout the study, to the extent possible. The LVEF abnormality status categories, as a change relative to LVEF at baseline, included: Increase or no change in LVEF; Decrease of <10 LVEF points; Absolute LVEF value ≥50% and a decrease of ≥10 LVEF points; and Absolute LVEF value <50% and a decrease of ≥10 LVEF points. The overall worst LVEF value was defined as the lowest post-baseline value up to the end of the study, including unscheduled assessments and the post-treatment period. | Safety population, which includes participants who received at least one dose of any study drug, with participants grouped according to the treatment received. Number analyzed indicates the number of participants with a baseline LVEF measurement and a post-baseline LVEF measurement at each time point. | Posted | Count of Participants | Participants | Baseline, Weeks 9, 18, 27, 36, 45, 54, 63, 72, 81, 90, 99, 108, 117, 126, 135, 144, 153, 162, 171, 180, 189, 198, 207, 216, and 225, Study Drug Discontinuation Visit (up to 4 years, 4 months), and Treatment-Free Follow-Up at 6 months, and 1 and 2 years |
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| Secondary | Baseline LVEF and Change From Baseline to Maximum On-Treatment Decrease in LVEF at Any Point During the Study | The baseline left ventricular ejection fraction (LVEF) and change from baseline to the maximum on-treatment decrease in LVEF at any point during the study are reported here. LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method should have been used throughout the study, to the extent possible. At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks. | Safety population, which includes participants who received at least one dose of any study drug, with participants grouped according to the treatment received. Number analyzed indicates participants with a baseline LVEF measurement and at least one post-baseline LVEF measurement, respectively. | Posted | Mean | Standard Deviation | percentage points of LVEF | Baseline and every 9 weeks from date of randomization until treatment discontinuation (up to 4 years, 4 months) |
|
From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months). At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: Placebo + Trastuzumab + Docetaxel | Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity. | 50 | 120 | 23 | 120 | 114 | 120 |
| EG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. | 40 | 122 | 30 | 122 | 119 | 122 |
| EG002 | Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. | 0 | 12 | 1 | 12 | 5 | 12 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Cardiac tamponade | Cardiac disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Ventricular arrhythmia | Cardiac disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Death | General disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Liver injury | Hepatobiliary disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
| |
| Fracture | Injury, poisoning and procedural complications | MedDRA v23.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Pelvic prolapse | Reproductive system and breast disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Large intestine polyp | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Peripheral arterial occlusive disease | Vascular disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
| |
| Gastrointestinal carcinoma in situ | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v23.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA v23.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Hypoproteinaemia | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Nail discolouration | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA v23.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v23.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v23.1 | Systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 28, 2018 | Jun 18, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077143 | Docetaxel |
| C485206 | pertuzumab |
| D000068878 | Trastuzumab |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Non-Visceral Disease |
|
| Estrogen and/or Progesterone Receptor Positive |
|
| Non-Measurable Disease |
|
| This was for the primary analysis. Hypothesis testing is considered exploratory in this bridging study. | Log Rank | This two-sided log-rank test was unstratified. | 0.0556 | Unstratified Hazard Ratio | 0.71 | 2-Sided | 95 | 0.50 | 1.01 | This unstratified Hazard Ratio (HR) is calculated as Arm B: Pertuzumab versus Arm A: Placebo. Cox proportional hazards model was used to estimate HR and its 95% CI. | Other |
| This was for the final analysis. Hypothesis testing is considered exploratory in this bridging study. | Log Rank | A two-sided log-rank test was used, stratified by disease type and hormone-receptor status. | 0.0008 | Stratified Hazard Ratio | 0.60 | 2-Sided | 95 | 0.45 | 0.81 | This stratified Hazard Ratio (HR) is calculated as Arm B: Pertuzumab versus Arm A: Placebo. Cox proportional hazards model, stratified by disease type and hormone-receptor status, was used to estimate HR and its 95% CI. | Other |
| This was for the final analysis. Hypothesis testing is considered exploratory in this bridging study. | Log Rank | This two-sided log-rank test was unstratified. | 0.0019 | Unstratified Hazard Ratio | 0.63 | 2-Sided | 95 | 0.47 | 0.85 | This unstratified Hazard Ratio (HR) is calculated as Arm B: Pertuzumab versus Arm A: Placebo. Cox proportional hazards model was used to estimate HR and its 95% CI. | Other |
| OG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
|
|
| OG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
|
|
|
| OG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
|
|
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity. Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. |
| OG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
|
|
|
| OG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
|
|
|
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
| OG002 | Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
|
|
| OG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
| OG002 | Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
|
|
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
| OG002 | Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
|
|
| OG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
| OG002 | Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| OG001 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel |
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
| OG002 | Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity. Following the primary analysis and upon approval of protocol version 4 (07-March-2020), the treatment assignment of participants in Arm A who were still on study treatment was unblinded, allowing the investigators to present those participants with the option to cross over and receive pertuzumab (in place of placebo) in addition to trastuzumab and docetaxel. |
| OG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| OG001 | Arm B: Pertuzumab + Trastuzumab + Docetaxel | Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity. |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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| Decrease <10 LVEF Points |
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| Absolute Value ≥50% & Decrease ≥10 LVEF Points |
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| Absolute Value <50% & Decrease ≥10 LVEF Points |
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