A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo (Blinded for Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane, as First Line Treatment in HER2 Positive Progressive or Recurrent Locally Advanced or Metastatic Breast Cancer

简要总结

主要结局

次要结局

• Percentage of Participants Who Died at 2 Years(From randomization until 2 years)
• Percentage of Participants Experiencing Treatment Failure(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014)
• Overall Survival (OS) at Clinical Cutoff(Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination))
• Percentage of Participants With Death or Disease Progression According to Investigator Assessment(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• One-Year Survival Rate(From randomization until 1 year)
• Overall Survival Truncated at 2 Years(From randomization until 2 years)
• PFS According to Investigator Assessment(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• Time to Treatment Failure (TTF)(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014)
• Percentage of Participants With Grade 5 Adverse Events(Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose))
• Hospitalization Days(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014)
• Percentage of Participants Who Died Prior to Clinical Cutoff(Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination))
• Percentage of Participants With Grade ≥3 Adverse Events(Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose)
• Percentage of Participants With Grade 3-4 Laboratory Parameters(Day 1, 8, and 15 of Cycle 1-3 and on Day 1 of each subsequent cycle up to 50 months from randomization until clinical cutoff of 16-Sept-2014)
• Percentage of Participants With a Clinically Significant Deterioration in Health Related Quality of Life (HRQoL) as Measured by FACT Breast (FACT-B) Trial Outcome Index-Physical Function Breast (TOI-PFB) Score(Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose))
• Percentage of Participants With Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status(Baseline, Day 1 of every Cycle up to Clinical Data Cut (up to 48 months))
• Percentage of Participants With Objective Response According to IRF Assessment(Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• Percentage of Participants Experiencing a Clinically Significant Increase in Taxane-Related Treatment Symptoms as Measured by Taxane Subscale of the Functional Assessment of Cancer Therapy (FACT) Taxane (FACT-TaxS) Score(Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose))
• Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module(At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2)
• Percentage of Participants With Hospitalization(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014)
• Percentage of Participants With Objective Response According to Investigator Assessment(Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module(At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2)
• Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score(Baseline, Cycle 7 (Week 18))
• Duration of Response According to IRF Assessment(Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) According to IRF Assessment(Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score(Baseline up to 39 months from randomization until clinical cutoff of 16-Sept-2014)
• Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score(Baseline, Cycle 7 (Week 18))
• Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With High Human Epidermal Growth Factor Receptor 2 (HER2) Messenger Ribonucleic Acid (mRNA) Levels(Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• PFS According to IRF Assessment Among Those With High HER2 mRNA Levels(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels(Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination))
• Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score(Baseline, Cycle 7 (Week 18))
• Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels(Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels(Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination))
• OS at Clinical Cutoff Among Those With High HER2 mRNA Levels(Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination))
• OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels(Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination))
• Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))
• PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose))