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| ID | Type | Description | Link |
|---|---|---|---|
| CLAP016A2302 | Other Identifier | Novartis |
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This was a randomized, double-blind, placebo-controlled, multicenter, Phase III study to evaluate and compare the efficacy and safety of Lapatinib + Paclitaxel versus Placebo + Paclitaxel in men and women with ErbB2 amplified metastatic (Stage IV) breast cancer who had not received prior therapy for metastatic disease.
Subjects were randomized to receive either Lapatinib (1500 mg once daily) + Paclitaxel (80 mg/m2 IV weekly for 3 weeks every 4 weeks) or Placebo (once daily) + Paclitaxel (80 mg/m2 IV weekly for 3 weeks every 4 weeks).
Subjects who progressed while on study and were on the placebo+paclitaxel arm were permitted to enter an extension phase of open label monotherapy therapy with lapatinib or open label combination therapy with lapatinib+paclitaxel and followed for response, progression and survival.
Based on the positive results in the primary analysis, Protocol Amendment 02 (dated 09 May 2011) discontinued further entry into the lapatinib monotherapy extension phase, and ongoing subjects taking placebo were permitted to replace it with open label lapatinib therapy (with or without continued paclitaxel therapy).
Following the primary Overall Survival (OS) analysis and subsequent implementation of Protocol Amendment 03, subjects who were still receiving active treatment entered the Long-term follow-up (LTFU) phase of the study. Reporting requirements in the LTFU phase were limited to Adverse events of special interest (AESI), Serious adverse events (SAEs) and pregnancy, and the subjects continued to receive treatment until the occurrence of unacceptable toxicity or disease progression (as determined by the investigator) or permanent withdrawal from treatment for any reason. Subjects who were no longer receiving active treatment were withdrawn from the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Paclitaxel and Lapatinib (Blinded) | Experimental | Paclitaxel and Lapatinib (Blinded) |
|
| Paclitaxel and Placebo (Blinded) | Active Comparator | Paclitaxel and Placebo (Blinded) |
|
| Open Label - Monotherapy (Extension Phase) | Other | Open Label - Monotherapy (Lapatinib) |
|
| Open Label - Combination Therapy (Extension Phase) | Other | Open Label - Combination Therapy (Lapatinib and Paclitaxel) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lapatinib (GW572016) oral tablets | Drug | 1500 mg oral daily continuously |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) at 53 Months | Overall Survival (OS) was defined as the interval of time (in months) between the date of randomization and the date of death due to any cause. | From date of randomization until date of death from any cause, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) at 190 Months | Overall Survival (OS) was defined as the interval of time (in months) between the date of randomization and the date of death due to any cause. | From date of randomization until date of death from any cause, assessed up to 190 months (Final OS analysis cut-off date = 23-Nov-2021) |
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Inclusion criteria:
Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases) Rapidly progressing or life threatening disease, as determined by the investigator Patients who received hormonal therapy and are no longer benefiting from this therapy and the hormonal treatment must have been stopped before the first dose of investigational treatment;
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Salvador | Estado de Bahia | 40.050-410 | Brazil | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25056500 | Derived | Xu B, Guan Z, Shen Z, Tong Z, Jiang Z, Yang J, DeSilvio M, Russo M, Leigh M, Ellis C. Association of phosphatase and tensin homolog low and phosphatidylinositol 3-kinase catalytic subunit alpha gene mutations on outcome in human epidermal growth factor receptor 2-positive metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone. Breast Cancer Res. 2014 Jul 24;16(4):405. doi: 10.1186/s13058-014-0405-y. | |
| 23509322 |
| Label | URL |
|---|---|
| Related Info | View source |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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This study was conducted in 43 centers in eight participating countries: Brazil (7), China (20), Hong Kong (3), Pakistan (3), Peru (1), Russian Federation (6), Thailand (2) and Ukraine (1).
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| ID | Title | Description |
|---|---|---|
| FG000 | Lapatinib 1500 mg + Paclitaxel | Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks |
| FG001 | Placebo + Paclitaxel |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Randomized Phase |
|
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| Paclitaxel infusion | Drug | Paclitaxel 80 mg/m2 every 3 weeks, 4th week rest for minimum 6 months |
|
| Placebo | Drug | Paclitaxel Matching Placebo |
|
| Progression-free Survival (PFS) by Investigator Assessment |
Progression-free survival (PFS) during the randomized phase was defined as the interval of time (in months) between the date of randomization and the earlier of date of disease progression (radiological or clinical assessment of symptomatic progression), or date of death due to any cause. |
| From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021) |
| Overall Response Rate (ORR) by Investigator Assessment | Overall response rate (ORR) during the randomized phase was evaluated per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and defined as the percentage of subjects achieving either a Complete Response (CR) or a Partial Response (PR). Participants with unknown or missing responses were treated as non-responders. | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021) |
| Clinical Benefit Rate (CBR) | Clinical benefit rate (CBR) was defined as the percentage of subjects with evidence of CR or PR or stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesions], taking as reference the smallest sum LD since treatment start) of >=24 weeks, based on confirmed responses from the investigator assessment of best overall response during the randomized phase. | From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary analysis cut-off date = 18-Jun-2010) |
| Duration of Response (DOR) | For subjects who show CR or PR, duration of response (DOR) was defined to be the time from first documented evidence of PR or CR until the first documented sign of disease progression (radiological or clinical assessment of symptomatic progression) or death due to any cause, if sooner during the randomized phase. | From date of confirmed CR or PR until date of progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021) |
| Number of Participants With a CR or PR at Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72 | The original outcome measure to be analyzed was Time to response (TTR) during the randomized phase defined as the time from randomization until first documented evidence of PR or CR (whichever status was recorded first); however, data were presented as the number of participants with a response at each nominal visit. Responses were based on the investigator's assessment, and only participants with a confirmed CR or PR were included in this analysis. | Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72 |
| Number of Tumors Evaluable for PIK3CA Mutations | Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. A PIK3CA mutation test kit was used to assess mutation status on genomic deoxyribonucleic acid (DNA) isolated from tumor tissue. | Baseline |
| Number of Participants With Tumors Evaluable for PTEN | Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. Immunohistochemistry (IHC) staining in an analytically validated assay was used in the assessment of PTEN protein expression on tumor tissue. Staining intensity was allocated a score of 0, 1+, 2+ or 3+. Tumors scored IHC 0 were considered as exhibiting an absence of PTEN expression whereas those scored ICH 1+, 2+ or 3+ were considered as exhibiting any PTEN expression, being 3+ the highest expression. | Baseline |
| Predictive Effect of PIK3CA Mutations Status on Overall Response Rate (ORR) | ORR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving either CR or PR. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. A PIK3CA mutation test kit was used to assess mutation status on genomic deoxyribonucleic acid (DNA) isolated from tumor tissue. | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
| Predictive Effect of PTEN Low on Overall Response Rate (ORR) | ORR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving either CR or PR. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. Immunohistochemistry (IHC) staining in an analytically validated assay was used in the assessment of PTEN protein expression on tumor tissue. Staining intensity was allocated a score of 0, 1+, 2+ or 3+. Tumors scored IHC 0 were considered as exhibiting an absence of PTEN expression whereas those scored ICH 1+, 2+ or 3+ were considered as exhibiting any PTEN expression, being 3+ the highest expression. Tumors scored IHC 0/1+ were considered PTEN low. | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
| Predictive Effect of PIK3CA Mutations Status on Clinical Benefit Rate (CBR) | CBR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving CR or PR or stable disease. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. A PIK3CA mutation test kit was used to assess mutation status on genomic deoxyribonucleic acid (DNA) isolated from tumor tissue. | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
| Predictive Effect of PTEN Low on Clinical Benefit Rate (CBR) | CBR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving CR or PR or stable disease. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. Immunohistochemistry (IHC) staining in an analytically validated assay was used in the assessment of PTEN protein expression on tumor tissue. Staining intensity was allocated a score of 0, 1+, 2+ or 3+. Tumors scored IHC 0 were considered as exhibiting an absence of PTEN expression whereas those scored ICH 1+, 2+ or 3+ were considered as exhibiting any PTEN expression, being 3+ the highest expression. Tumors scored IHC 0/1+ were considered PTEN low. | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
| Salvador |
| Estado de Bahia |
| 40285-001 |
| Brazil |
| Novartis Investigative Site | Belo Horizonte | Minas Gerais | 30150-281 | Brazil |
| Novartis Investigative Site | Natal | Rio Grande do Norte | 59075-740 | Brazil |
| Novartis Investigative Site | Porto Alegre | Rio Grande do Sul | 90610 000 | Brazil |
| Novartis Investigative Site | Jaú | São Paulo | 17210-120 | Brazil |
| Novartis Investigative Site | Santo André | São Paulo | 09060-650 | Brazil |
| Novartis Investigative Site | São Paulo | São Paulo | 01221-020 | Brazil |
| Novartis Investigative Site | São Paulo | São Paulo | 03102-002 | Brazil |
| Novartis Investigative Site | Guangzhou | Guangdong | 510060 | China |
| Novartis Investigative Site | Wuhan | Hubei | 430030 | China |
| Novartis Investigative Site | Nanjing | Jiangsu | 210002 | China |
| Novartis Investigative Site | Nanjing | Jiangsu | 210009 | China |
| Novartis Investigative Site | Dalian | Liaoning | 116027 | China |
| Novartis Investigative Site | Xi'an | Shaanxi | 710032 | China |
| Novartis Investigative Site | Xi'an | Shaanxi | 710061 | China |
| Novartis Investigative Site | Jinan | Shandong | 250012 | China |
| Novartis Investigative Site | Jinan | Shandong | 250031 | China |
| Novartis Investigative Site | Jinan | Shandong | 250117 | China |
| Novartis Investigative Site | Hangzhou | Zhejiang | 310022 | China |
| Novartis Investigative Site | Beijing | 100021 | China |
| Novartis Investigative Site | Beijing | 100036 | China |
| Novartis Investigative Site | Beijing | 100071 | China |
| Novartis Investigative Site | Beijing | 100853 | China |
| Novartis Investigative Site | Chengdu | 610041 | China |
| Novartis Investigative Site | Chongqing | 400037 | China |
| Novartis Investigative Site | Dalian | 116011 | China |
| Novartis Investigative Site | Fuzhou | 350001 | China |
| Novartis Investigative Site | Fuzhou | 350014 | China |
| Novartis Investigative Site | Shanghai | 200032 | China |
| Novartis Investigative Site | Shanghai | 200070 | China |
| Novartis Investigative Site | Shanghai | 200433 | China |
| Novartis Investigative Site | Shenyang | 110015 | China |
| Novartis Investigative Site | Tianjin | 300060 | China |
| Novartis Investigative Site | Kowloon | Hong Kong |
| Novartis Investigative Site | Pokfulam | Hong Kong |
| Novartis Investigative Site | Tuenmen | Hong Kong |
| Novartis Investigative Site | Lahore | 53400 | Pakistan |
| Novartis Investigative Site | Lahore | 54600 | Pakistan |
| Novartis Investigative Site | Lahore | Pakistan |
| Novartis Investigative Site | Lima | Lima 34 | Peru |
| Novartis Investigative Site | Kazan' | 420029 | Russia |
| Novartis Investigative Site | Moscow | 117997 | Russia |
| Novartis Investigative Site | Moscow | 125101 | Russia |
| Novartis Investigative Site | Moscow | 143423 | Russia |
| Novartis Investigative Site | Rostov-on-Don | 344037 | Russia |
| Novartis Investigative Site | Samara | 443031 | Russia |
| Novartis Investigative Site | Voronezh | 394062 | Russia |
| Novartis Investigative Site | Bangkok | 10400 | Thailand |
| Novartis Investigative Site | Chiang Mai | 50200 | Thailand |
| Novartis Investigative Site | Cherkasy | 18009 | Ukraine |
| Novartis Investigative Site | Chernihiv | 14029 | Ukraine |
| Novartis Investigative Site | Dnipropetrovsk | 49055 | Ukraine |
| Novartis Investigative Site | Zaporizhzhia | 69040 | Ukraine |
| Derived |
| Guan Z, Xu B, DeSilvio ML, Shen Z, Arpornwirat W, Tong Z, Lorvidhaya V, Jiang Z, Yang J, Makhson A, Leung WL, Russo MW, Newstat B, Wang L, Chen G, Oliva C, Gomez H. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. J Clin Oncol. 2013 Jun 1;31(16):1947-53. doi: 10.1200/JCO.2011.40.5241. Epub 2013 Mar 18. |
Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks
| FG002 | Open Label - Monotherapy | Open Label - Monotherapy (Lapatinib) |
| FG003 | Open Label - Combination Therapy | Open Label - Combination Therapy (Lapatinib and Paclitaxel) |
|
| Safety Population | All randomized subjects who received at least one dose of study medication |
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| COMPLETED |
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| NOT COMPLETED |
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| Open Label Phase |
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| ID | Title | Description |
|---|---|---|
| BG000 | Lapatinib 1500 mg + Paclitaxel | Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks |
| BG001 | Placebo + Paclitaxel | Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Number | Participants |
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| Number of participants with any visceral metastatic disease and with only non-visceral disease | Metastasis is defined as the spread of a tumor or cancerous cells from the primary site to one or more sites elsewhere in the body. Visceral metastasis is defined as the spread of cancer to viscera, the internal organs of the body, specifically those within the chest (as the heart or lungs) or abdomen (as the liver, pancreas, or intestines). Non-visceral organs are defined as any organ not considered visceral. | Count of Participants | Participants |
| |||||||||||||||
| Number of Participants with the Indicated Hormone Receptor Status | Cancer cells have hormone receptor expression of Estrogen Receptor (ER) and/or Progesterone Receptor (PR) and are thus considered to be ER+ and/or PgR+ cells, respectively. | Count of Participants | Participants |
| |||||||||||||||
| Number of Participants with the Indicated Stage of Disease at Initial Diagnosis | The stage of cancer is a description of the extent to which the cancer has spread. Stage I cancer is localized; Stage II cancer has not started to spread into the surrounding tissue, but the tumor is larger than in Stage I; Stage III cancer is locally advanced and/or involves local lymph nodes; Stage IV cancer has spread to other organs. | Count of Participants | Participants |
| |||||||||||||||
| Number of Participants with the Indicated Eastern Cooperative Oncology Group Performance Status | Eastern Cooperative Oncology Group (ECOG) Performance Status classifies participants according to their functional impairment, and scores indicate: 0, fully active; 1, ambulatory, restricted strenuous activity; 2, ambulatory, no work activity; 3, partially confined to bed; 4, totally confined in bed; 5, death. Participants were required to have a baseline ECOG performance status of 0 or 1 for study participation. | Count of Participants | Participants |
| |||||||||||||||
| Number of Participants with the Indicated Number of Metastatic Sites | Tumor cells move from the primary site to other sites in the body, where they continue to multiply and eventually form another clinically detectable tumor; thus, the site becomes metastatic. The table indicates number of metastatic sites. | Count of Participants | Participants |
| |||||||||||||||
| Mean Time of Disease-Free Interval | The disease-free interval was defined as the time from initial diagnosis to metastases | Mean | Standard Deviation | months |
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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 | Overall Survival (OS) at 53 Months | Overall Survival (OS) was defined as the interval of time (in months) between the date of randomization and the date of death due to any cause. | Intent-to-Treat (ITT) Population. The ITT population was comprised of all randomized subjects and was based on the treatment to which the subject was randomized. | Posted | Median | 95% Confidence Interval | months | From date of randomization until date of death from any cause, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
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| Secondary | Overall Survival (OS) at 190 Months | Overall Survival (OS) was defined as the interval of time (in months) between the date of randomization and the date of death due to any cause. | Intent-to-Treat (ITT) Population. The ITT population was comprised of all randomized subjects and was based on the treatment to which the subject was randomized. | Posted | Median | 95% Confidence Interval | months | From date of randomization until date of death from any cause, assessed up to 190 months (Final OS analysis cut-off date = 23-Nov-2021) |
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| Secondary | Progression-free Survival (PFS) by Investigator Assessment | Progression-free survival (PFS) during the randomized phase was defined as the interval of time (in months) between the date of randomization and the earlier of date of disease progression (radiological or clinical assessment of symptomatic progression), or date of death due to any cause. | Intent-to-Treat (ITT) Population. The ITT population was comprised of all randomized subjects and was based on the treatment to which the subject was randomized. | Posted | Median | 95% Confidence Interval | months | From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021) |
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| Secondary | Overall Response Rate (ORR) by Investigator Assessment | Overall response rate (ORR) during the randomized phase was evaluated per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and defined as the percentage of subjects achieving either a Complete Response (CR) or a Partial Response (PR). Participants with unknown or missing responses were treated as non-responders. | Intent-to-Treat (ITT) Population. The ITT population was comprised of all randomized subjects and was based on the treatment to which the subject was randomized. | Posted | Number | 95% Confidence Interval | Percentage of Participants | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021) |
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| Secondary | Clinical Benefit Rate (CBR) | Clinical benefit rate (CBR) was defined as the percentage of subjects with evidence of CR or PR or stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesions], taking as reference the smallest sum LD since treatment start) of >=24 weeks, based on confirmed responses from the investigator assessment of best overall response during the randomized phase. | Intent-to-Treat (ITT) Population. The ITT population was comprised of all randomized subjects and was based on the treatment to which the subject was randomized. | Posted | Number | 95% Confidence Interval | Percentage of Participants | From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary analysis cut-off date = 18-Jun-2010) |
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| Secondary | Duration of Response (DOR) | For subjects who show CR or PR, duration of response (DOR) was defined to be the time from first documented evidence of PR or CR until the first documented sign of disease progression (radiological or clinical assessment of symptomatic progression) or death due to any cause, if sooner during the randomized phase. | Subset of participants in the Intent-to-Treat (ITT) Population with a confirmed CR or PR | Posted | Median | 95% Confidence Interval | months | From date of confirmed CR or PR until date of progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021) |
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| Secondary | Number of Participants With a CR or PR at Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72 | The original outcome measure to be analyzed was Time to response (TTR) during the randomized phase defined as the time from randomization until first documented evidence of PR or CR (whichever status was recorded first); however, data were presented as the number of participants with a response at each nominal visit. Responses were based on the investigator's assessment, and only participants with a confirmed CR or PR were included in this analysis. | Participants in the Intent-to-Treat (ITT) Population with a confirmed CR or PR | Posted | Number | Participants | Weeks 8, 12, 16, 24, 32, 40, 48, 56, 64, and 72 |
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| Secondary | Number of Tumors Evaluable for PIK3CA Mutations | Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. A PIK3CA mutation test kit was used to assess mutation status on genomic deoxyribonucleic acid (DNA) isolated from tumor tissue. | Participants in the Intent-to-Treat (ITT) Population with tumors evaluable for PIK3CA mutations | Posted | Count of Participants | Participants | Baseline |
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| Secondary | Number of Participants With Tumors Evaluable for PTEN | Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. Immunohistochemistry (IHC) staining in an analytically validated assay was used in the assessment of PTEN protein expression on tumor tissue. Staining intensity was allocated a score of 0, 1+, 2+ or 3+. Tumors scored IHC 0 were considered as exhibiting an absence of PTEN expression whereas those scored ICH 1+, 2+ or 3+ were considered as exhibiting any PTEN expression, being 3+ the highest expression. | Participants in the Intent-to-Treat (ITT) Population with tumors evaluable for PTEN | Posted | Count of Participants | Participants | Baseline |
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| Secondary | Predictive Effect of PIK3CA Mutations Status on Overall Response Rate (ORR) | ORR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving either CR or PR. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. A PIK3CA mutation test kit was used to assess mutation status on genomic deoxyribonucleic acid (DNA) isolated from tumor tissue. | Participants in the Intent-to-Treat (ITT) Population with tumors evaluable for PIK3CA mutations (PIK3CA mutation and PIK3CA wild type) | Posted | Number | percentage of participants | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
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| Secondary | Predictive Effect of PTEN Low on Overall Response Rate (ORR) | ORR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving either CR or PR. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. Immunohistochemistry (IHC) staining in an analytically validated assay was used in the assessment of PTEN protein expression on tumor tissue. Staining intensity was allocated a score of 0, 1+, 2+ or 3+. Tumors scored IHC 0 were considered as exhibiting an absence of PTEN expression whereas those scored ICH 1+, 2+ or 3+ were considered as exhibiting any PTEN expression, being 3+ the highest expression. Tumors scored IHC 0/1+ were considered PTEN low. | Participants in the Intent-to-Treat (ITT) Population with PTEN low and without PTEN low | Posted | Number | percentage of participants | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Predictive Effect of PIK3CA Mutations Status on Clinical Benefit Rate (CBR) | CBR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving CR or PR or stable disease. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. A PIK3CA mutation test kit was used to assess mutation status on genomic deoxyribonucleic acid (DNA) isolated from tumor tissue. | Participants in the Intent-to-Treat (ITT) Population with tumors evaluable for PIK3CA mutations (PIK3CA mutation and PIK3CA wild type) | Posted | Number | percentage of participants | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Predictive Effect of PTEN Low on Clinical Benefit Rate (CBR) | CBR was evaluated per RECIST v1.1 and defined as the percentage of subjects achieving CR or PR or stable disease. Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) was studied to evaluate the predictive and prognostic value of PIK3CA mutations and/or PTEN low in HER2-positive patients receiving first-line treatment with paclitaxel alone or in combination with lapatinib. Immunohistochemistry (IHC) staining in an analytically validated assay was used in the assessment of PTEN protein expression on tumor tissue. Staining intensity was allocated a score of 0, 1+, 2+ or 3+. Tumors scored IHC 0 were considered as exhibiting an absence of PTEN expression whereas those scored ICH 1+, 2+ or 3+ were considered as exhibiting any PTEN expression, being 3+ the highest expression. Tumors scored IHC 0/1+ were considered PTEN low. | Participants in the Intent-to-Treat (ITT) Population with PTEN low and without PTEN low | Posted | Number | percentage of participants | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010) |
|
From study treatment start date till 30 days safety follow-up, assessed up to 190 months (Final OS analysis cut-off date = 23-Nov-2021)
Any sign or symptom that occurs during the treatment period plus 30 days post-treatment. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
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 | Lapatinib 1500 mg + Paclitaxel | Lapatinib 1500 milligrams (mg) administered once daily plus paclitaxel 80 mg/meters squared (m^2) administered intravenously (IV) weekly for 3 weeks every 4 weeks | 10 | 222 | 67 | 222 | 219 | 222 |
| EG001 | Placebo + Paclitaxel | Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks | 15 | 221 | 30 | 221 | 206 | 221 |
| EG002 | Open Label - Monotherapy | Open Label - Monotherapy (Lapatinib) | 2 | 149 | 8 | 149 | 86 | 149 |
| EG003 | Open Label - Combination Therapy | Open Label - Combination Therapy (Lapatinib and Paclitaxel) | 0 | 4 | 0 | 4 | 3 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Granulocytopenia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Cardiac failure chronic | Cardiac disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Lithiasis | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hepatobiliary disease | Hepatobiliary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hepatotoxicity | Hepatobiliary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Pyelonephritis acute | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (24.1) | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Breast neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.1) | Systematic Assessment |
| |
| Thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.1) | Systematic Assessment |
| |
| Intracranial pressure increased | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Completed suicide | Psychiatric disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Laryngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (24.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Granulocytopenia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Mucosal erosion | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Red blood cell count decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
|
The data collected for China patients after 01JUL2019 were excluded from analysis due to local regulations in China.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
| 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 |
|---|---|
| D000077341 | Lapatinib |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Disease progression |
|
| Physician Decision |
|
| Relocation of patient |
|
| Reason for withdrawal unspecified |
|
| Male |
|
| Asian |
|
| Hispanic |
|
| Other |
|
| Non-visceral |
|
| ER- and PgR- |
|
| Stage III |
|
| Stage IV |
|
| Unknown |
|
| 1, Ambulatory, Restricted Strenuous Activity |
|
| Less than 3 |
|
|
|
| Participants |
|
|
|
| Participants |
|
|
|
|
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks |
|
|
|
|
|
Matching placebo administered once daily plus paclitaxel 80 mg/m^2 administered IV weekly for 3 weeks every 4 weeks |
|
|
|