A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)

• ClinicalTrials.gov Identifier: NCT01120184
• Recruitment Status: Completed
• First Posted: May 10, 2010
• Results First Posted: February 23, 2017
• Last Update Posted: November 7, 2017
• Sponsor: Hoffmann-La Roche
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This randomized, 3-arm, multicenter, phase III study will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) with pertuzumab or trastuzumab emtansine (T-DM1) with pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab (Herceptin) plus taxane (docetaxel or paclitaxel) in participants with HER2-positive progressive or recurrent locally advanced or previously untreated metastatic breast cancer. Participants will be randomized to 1 of 3 treatment arms (Arms A, B or C). Arm A will be open-label, whereas Arms B and C will be blinded.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: docetaxel; Drug: paclitaxel; Drug: pertuzumab; Drug: pertuzumab-placebo; Drug: trastuzumab [Herceptin]; Drug: trastuzumab emtansine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1095 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 31, 2010
• Actual Primary Completion Date: September 30, 2014
• Actual Study Completion Date: September 16, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Trastuzumab + Taxane (docetaxel or paclitaxel)	Drug: docetaxel; 75 mg/m2 or 100 mg/m2 intravenously every 3 weeks for a minimum of 6 cycles.; Drug: paclitaxel; 80 mg/m2 intravenously weekly for a minimum of 18 weeks; Drug: trastuzumab [Herceptin]; trastuzumab [Herceptin] doses when administered with docetaxel: 8 mg/kg intravenously on cycle 1 followed by 6 mg/kg every 3 weeks in subsequent cycles or trastuzumab (Herceptin) doses when administered with paclitaxel: 4 mg/kg intravenously on day 1 of cycle 1 followed by 2 mg/kg weekly starting on day 8 of cycle 1.
Experimental: Trastuzumab emtansine + pertuzumab	Drug: pertuzumab; 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles; Drug: trastuzumab emtansine; 3.6 mg/kg intravenously every 3 weeks
Experimental: Trastuzumab emtansine + pertuzumab placebo	Drug: pertuzumab-placebo; 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles; Drug: trastuzumab emtansine; 3.6 mg/kg intravenously every 3 weeks

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment [ Time Frame: 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) ]
   Tumor assessments were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a greater than or equal to (≥) 20 percent (%) and 5-millimeter (mm) increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.
2. Progression-Free Survival (PFS) According to IRF Assessment [ Time Frame: 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) ]
   Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis, and corresponding confidence intervals (CIs) were computed using the Brookmeyer-Crowley method.

Secondary Outcome Measures :

1. Percentage of Participants Who Died Prior to Clinical Cutoff [ Time Frame: 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) ]
   The percentage of participants who died prior to clinical cutoff was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.
2. Overall Survival (OS) at Clinical Cutoff [ Time Frame: 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 was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.
3. Percentage of Participants With Death or Disease Progression According to Investigator Assessment [ Time Frame: 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) ]
   Tumor assessments were performed by the investigator according to RECIST version 1.1. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.
4. PFS According to Investigator Assessment [ Time Frame: 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) ]
   Tumor assessments were performed by the investigator according to RECIST version 1.1. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.
5. Percentage of Participants Experiencing Treatment Failure [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]
   Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. The percentage of participants with treatment failure was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.
6. Time to Treatment Failure (TTF) [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]
   Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. TTF was defined as the time from randomization to treatment failure. Median TTF was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.
7. One-Year Survival Rate [ Time Frame: From randomization until 1 year ]
   The percentage of participants alive at 1 year after randomization was estimated as the one-year survival rate using Kaplan-Meier analysis, and corresponding CIs were computed using Greenwood's estimate of the standard error.
8. Percentage of Participants With Grade ≥3 Adverse Events [ Time Frame: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose ]
   Adverse events were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival. Grade 5: Death.
9. Percentage of Participants Who Died at 2 Years [ Time Frame: From randomization until 2 years ]
10. Overall Survival Truncated at 2 Years [ Time Frame: From randomization until 2 years ]
    Overall Survival truncated at 2 years was defined as the percentage of participants alive at 2 years.
11. Percentage of Participants With Grade 5 Adverse Events [ Time Frame: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose) ]
    Adverse events were graded according to NCI CTCAE version 4.0. Grade 5 adverse events are those events which led to death.
12. Percentage of Participants With Grade 3-4 Laboratory Parameters [ Time Frame: 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 ]
    Laboratory results were graded according to NCI CTCAE version 4.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival.
13. Percentage of Participants With Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline, Day 1 of every Cycle up to Clinical Data Cut (up to 48 months) ]
    The ECOG performance status is a scale used to quantify cancer participants' general well-being and activities of daily life. The scale ranges from 0 to 5, with 0 denoting perfect health and 5 indicating death. The 6 categories are 0=Asymptomatic (Fully active, able to carry on all predisease activities without restriction), 1=Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2=Symptomatic, < 50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours), 3=Symptomatic, > 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours), 4=Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair), 5=Death.
14. Hospitalization Days [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]
    Hospitalization was defined as a non-administration-related hospitalization due to serious adverse event, while on study treatment. Reported values represent number of days admitted per participants.
15. Percentage of Participants With Hospitalization [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]
    Hospitalization was defined as a non-administration-related hospitalization due to serious adverse event, while on study treatment.
16. Percentage of Participants With Objective Response According to IRF Assessment [ Time Frame: 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) ]
    Objective response was defined as having complete response (CR) or partial response (PR), assessed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the objective response rate [ORR]) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. Corresponding CIs were computed using the Blyth-Still-Casella exact method.
17. Percentage of Participants With Objective Response According to Investigator Assessment [ Time Frame: 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) ]
    Objective response was defined as having CR or PR, assessed according to RECIST version 1.1, by investigator. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the ORR) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. Corresponding CIs were computed using the Blyth-Still-Casella exact method.
18. Duration of Response According to IRF Assessment [ Time Frame: 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) ]
    Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Duration of response was defined as the time from confirmed PR or CR to first documented disease progression or death from any cause. CR was defined as the disappearance of all target lesions and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. Median duration of response was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.
19. Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) According to IRF Assessment [ Time Frame: 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) ]
    Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient (20%) increase to qualify for disease progression. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR, PR, or SD was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100.
20. 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 [ Time Frame: 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) ]
    The FACT-Taxane is a self-reported instrument which measures the health-related quality of life (HRQOL) of participants receiving taxane-containing chemotherapy. The FACT-TaxS consists of 16 items including 11 neurotoxicity-related questions and 5 additional questions assessing arthralgia, myalgia, and skin discoloration. Items are rated from 0 (not at all) to 4 (very much) and a total score is inversely derived. Scores may range from 0 to 64, with higher scores indicating fewer/no symptoms. A minimally clinically important difference in treatment-related symptoms was defined as a ≥5% decrease (ie, 3.2 points) in FACT-TaxS score from Baseline. The percentage of participants with treatment-related symptoms was calculated using following formula: [number of participants meeting the above threshold divided by the number analyzed] multiplied by 100. Corresponding CIs were computed using the Blyth-Still-Casella exact method.
21. Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module [ Time Frame: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2 ]
    The FACT-C is a self-reported instrument which measures HRQOL pertaining to colorectal cancer. Response options on each question may range from 0 (not at all) to 4 (very much). The percentage of participants with nausea was calculated using following formula: [number of participants with any level of either symptom divided by the number analyzed] multiplied by 100.
22. Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module [ Time Frame: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2 ]
    The FACT-C is a self-reported instrument which measures HRQOL pertaining to colorectal cancer. Response options on each question may range from 0 (not at all) to 4 (very much). The percentage of participants with diarrhea was calculated using following formula: [number of participants with any level of either symptom divided by the number analyzed] multiplied by 100.
23. 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 [ Time Frame: 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) ]
    The FACT-B is a self-reported instrument which measures HRQOL of participants with breast cancer. It consists of 5 subscales including physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and a breast cancer subscale (BCS). The TOI-PFB score is taken by adding the scores from the PWB (7 items), FWB (7 items), and BCS (9 items) subscales. Items are rated from 0 (not at all) to 4 (very much) and a total score is derived. Scores may range from 0 to 92, with higher scores indicating better HRQOL. A 5 point change has been identified as the clinically minimal important difference (CMID) on the FACT-TOI-PFB scale. The percentage of participants with deterioration was calculated as [number of participants meeting the above threshold divided by the number analyzed] multiplied by 100.
24. Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score [ Time Frame: Baseline up to 39 months from randomization until clinical cutoff of 16-Sept-2014 ]
    The FACT-B is a self-reported instrument which measures HRQOL of participants with breast cancer. It consists of 5 subscales including PWB, SWB, EWB, FWB, and BCS. The TOI-PFB score is taken by adding the scores from the PWB (7 items), FWB (7 items), and BCS (9 items) subscales. Items are rated from 0 (not at all) to 4 (very much) and a total score is derived. Scores may range from 0 to 92, with higher scores indicating better HRQOL. A 5 point change has been identified as the clinically minimal important difference (CMID) on the FACT-TOI-PFB scale. Time to deterioration was defined as the time from Baseline until the first decrease in FACT-B TOI-PFB score. Median time to deterioration was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.
25. Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score [ Time Frame: Baseline, Cycle 7 (Week 18) ]
    The RSCL is a self-reported instrument which consists of 4 domains including physical symptom distress, psychological distress, activity level, and overall global life quality. Only the activity level scale was collected and assessed. Scores may range from 0 to 100, with higher scores indicating increased burden of disease. Mean RSCL activity scale score changes were calculated as [mean score at the assessment visit minus mean score at Baseline]. The higher the score, the higher the level of impairment or burden.
26. Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score [ Time Frame: Baseline, Cycle 7 (Week 18) ]
    The WPAI is a patient-reported measure which assesses the effect of general health and symptom severity on work productivity and regular activities. The General Health questionnaire asks participants to estimate the number of hours missed from work due to reasons related and unrelated to their health problems, as well as the total number of hours actually worked in the preceding 7-day period. The percentage of participants reporting that they were employed (working for pay) was assessed at baseline was assessed along with Absenteeism (work time missed), Presenteeism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. The reported changes represent change from baseline at Cycle 7. The score range for the scales of the WPAI is between 0 (no effect) to 100% (max effect)
27. Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score [ Time Frame: Baseline, Cycle 7 (Week 18) ]
    The WPAI is a patient-reported measure which assesses the effect of general health and symptom severity on work productivity and regular activities. The General Health questionnaire asks participants to estimate the number of hours missed from work due to reasons related and unrelated to their health problems, as well as the total number of hours actually worked in the preceding 7-day period. The percentage of participants reporting that they were employed (working for pay) was assessed at baseline was assessed along with Absenteeism (work time missed), Presenteeism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. The reported changes represent change from baseline at Cycle 7. The score range for the scales of the WPAI is between 0 (no effect) to 100% (max effect).
28. 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 [ Time Frame: 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) ]
    Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the ORR) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100.
29. Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels [ Time Frame: 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) ]
    Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the ORR) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100.
30. Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels [ Time Frame: 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) ]
    Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.
31. PFS According to IRF Assessment Among Those With High HER2 mRNA Levels [ Time Frame: 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) ]
    Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis.
32. Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels [ Time Frame: 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) ]
    Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.
33. PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels [ Time Frame: 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) ]
    Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis.
34. Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels [ Time Frame: 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) ]
    The percentage of participants who died prior to clinical cutoff was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.
35. OS at Clinical Cutoff Among Those With High HER2 mRNA Levels [ Time Frame: 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 was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis.
36. Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels [ Time Frame: 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) ]
    The percentage of participants who died prior to clinical cutoff was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.
37. OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels [ Time Frame: 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 was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis. Reported upper bound of confidence interval for "Trastuzumab Emtansine + Placebo" and confidence interval values for "Trastuzumab + Taxane" and "Trastuzumab Emtansine + Pertuzumab" are censored values.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adult participants >/=18 years of age
• HER2-positive breast cancer
• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and be a candidate for chemotherapy. Participants with locally advanced disease must have recurrent or progressive disease, which must not be amenable to resection with curative intent.
• Participants must have measurable and/or non-measurable disease which must be evaluable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Adequate organ function as determined by laboratory results

Exclusion Criteria:

• History of prior (or any) chemotherapy for metastatic breast cancer or recurrent locally advanced disease
• An interval of <6 months from the last dose of vinca-alkaloid or taxane cytotoxic chemotherapy until the time of metastatic diagnosis
• Hormone therapy <7 days prior to randomization
• Trastuzumab therapy and/or lapatinib (neo- or adjuvant setting) <21 days prior to randomization
• Prior trastuzumab emtansine or pertuzumab therapy

Contacts and Locations

Locations

United States, Arizona

Arizona Oncology

Tucson, Arizona, United States, 85704

United States, Arkansas

Uni of Arkansas For Medical Sciences; Arkansas Cancer Research Center

Little Rock, Arkansas, United States, 72204

Little Rock Hematology Oncology Associates, PA

Little Rock, Arkansas, United States, 72205

United States, California

Scripps Cancer Center

La Jolla, California, United States, 92037

University of California; Moores Cancer Center

La Jolla, California, United States, 92093

Clnc L Trials & Rsch Assoc-Inc

Montebello, California, United States, 90640

Global Oncology, Inc.

Monterey Park, California, United States, 91754

Southern California Kaiser Permanente

San Diego, California, United States, 92108

Sharp Healthcare; Oncology Research Program

San Diego, California, United States, 92123

Breastlink Medical Group Inc

Santa Ana, California, United States, 92705

Kaiser Permanente; Oncology Clinical Trials

Vallejo, California, United States, 94589

United States, Colorado

Uni of Colorado Cancer Center; Anschutz Cancer Pavilion

Aurora, Colorado, United States, 80045

United States, Connecticut

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, United States, 06510

United States, Delaware

Christiana Care Health Srvcs

Newark, Delaware, United States, 19713

United States, District of Columbia

Washington Cancer Institute; Washington Hospital Center

Washington, District of Columbia, United States, 20010

United States, Florida

Innovative Medical Research of South Florida

Aventura, Florida, United States, 33180

Northwest Oncology/ Hematology Assoc.

Coral Springs, Florida, United States, 33065-5701

Florida Cancer Specialists; SCRI

Fort Myers, Florida, United States, 33901

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States, 32224

Hematology Oncology Associates

Loxahatchee, Florida, United States, 33470

Uni of Miami School of Medicine; Sylvester Comprehensive Cancer Center

Miami, Florida, United States, 33136

United States, Georgia

University Cancer & Blood Center, LLC

Athens, Georgia, United States, 30607

Northeast Georgia Medical Center; Oncology Research Dept-5C

Gainesville, Georgia, United States, 30501

United States, Hawaii

Cancer Research Center of Hawaii; Clinical Sciences

Honolulu, Hawaii, United States, 96813

United States, Idaho

Mountain States Tumor Inst.

Boise, Idaho, United States, 83712

United States, Illinois

Uni of Chicago

Chicago, Illinois, United States, 60637

Decatur Memorial Hospital

Decatur, Illinois, United States, 62526

Ingalls Memorial Hospital

Harvey, Illinois, United States, 60426

Loyola University Med Center

Maywood, Illinois, United States, 60153

Illinois Cancer Care

Peoria, Illinois, United States, 61615

Carle Cancer Center

Urbana, Illinois, United States, 61801

United States, Indiana

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States, 46202

Horizon Oncology Research, Inc.

Lafayette, Indiana, United States, 47905

United States, Iowa

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, United States, 52403

Siouxland Hematology/Oncology

Sioux City, Iowa, United States, 51101

United States, Kentucky

James Graham Brown Cancer Center, University of Louisville

Louisville, Kentucky, United States, 40202

United States, Maine

New England Cancer Specialists

Scarborough, Maine, United States, 04074

York Hospital

York, Maine, United States, 03909

United States, Maryland

Anne Arundel Health System Research Instit-Annapolis Oncology Ctr

Annapolis, Maryland, United States, 21401

Mercy Medical Center; Medical Oncology & Hematology

Baltimore, Maryland, United States, 21202

Suburban Hospital

Bethesda, Maryland, United States, 20817

United States, Massachusetts

Boston Medical Center

Boston, Massachusetts, United States, 02118

United States, Michigan

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

Spectrum Health Grand Rapids

Grand Rapids, Michigan, United States, 49503

United States, Minnesota

St. Mary's Duluth Clinic Heath System

Duluth, Minnesota, United States, 55805

University of Minnesota.

Minneapolis, Minnesota, United States, 55454

Mayo Clinic Rochester

Rochester, Minnesota, United States, 55902

Metro-Minnesota CCOP

Saint Louis Park, Minnesota, United States, 55416

United States, Missouri

Columbia Comprehensive Cancer Center Clinic

Jefferson City, Missouri, United States, 65109

St. John'S Mercy Medical Center; David C. Pratt Cancer Center

Saint Louis, Missouri, United States, 63141

Mercy Clinic Cancer & Hematology

Springfield, Missouri, United States, 65804

United States, Nebraska

Nebraska Methodist Hospital; Cancer Center

Omaha, Nebraska, United States, 68114

United States, New Hampshire

Dartmouth Hitchcock Med Center

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Hackensack Uni Medical Center; Northern Nj Cancer Center

Hackensack, New Jersey, United States, 07601

Cancer Inst. of New Jersey

New Brunswick, New Jersey, United States, 08901

United States, New Mexico

Presbyterian Medical Group

Albuquerque, New Mexico, United States, 87110

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87131-0001

San Juan Oncology Associates

Farmington, New Mexico, United States, 87401

United States, New York

New York Oncology Hematology, P.C.

Albany, New York, United States, 12208

Queens Medical Associates

Fresh Meadows, New York, United States, 11366

Queens Hospital Center

Jamaica, New York, United States, 11432

Arena Oncology Associates

Lake Success, New York, United States, 11042

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Weill Medical College of Cornell Uni

New York, New York, United States, 10065

United States, North Carolina

Carolinas Hem-Oncology Assoc

Charlotte, North Carolina, United States, 28203

Carolina Oncology Specialists, PA - Hickory

Hickory, North Carolina, United States, 28602

Marion L. Shepard Cancer Center

Washington, North Carolina, United States, 27889

United States, North Dakota

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States, 58122-9988

United States, Ohio

Oncology Hematology Care - SCRI

Cincinnati, Ohio, United States, 45242

United States, Oregon

Providence Portland Medical Ctr

Portland, Oregon, United States, 97225

United States, Pennsylvania

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States, 17033

United States, Rhode Island

Pharma Resource

East Providence, Rhode Island, United States, 02915

United States, South Carolina

Charleston Hematology Oncology

Charleston, South Carolina, United States, 29414

Medical University of SC (MUSC)

Charleston, South Carolina, United States, 29425

South Carolina Oncology Associates - SCRI

Columbia, South Carolina, United States, 29210

United States, South Dakota

Avera Cancer Institute

Sioux Falls, South Dakota, United States, 57105

United States, Tennessee

SCRI Tennessee Oncology Chattanooga

Chattanooga, Tennessee, United States, 37404

West Clinic

Germantown, Tennessee, United States, 38138

Uni of Tennessee Cancer Inst.

Memphis, Tennessee, United States, 38104

Tennessee Onc., PLLC - SCRI

Nashville, Tennessee, United States, 37203

Vanderbilt-Ingram Cancer Ctr

Nashville, Tennessee, United States, 37232

United States, Texas

The Don & Sybil Harrington Cancer Center; Department of Clinical Research

Amarillo, Texas, United States, 79106

Uni of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390-9063

Uni of Texas - Md Anderson Cancer Center; Dept of Breast Medical Oncology

Houston, Texas, United States, 77030

Cancer Care Centers of South Texas

San Antonio, Texas, United States, 78217

United States, Utah

Northern Utah Associates

Ogden, Utah, United States, 84403

United States, Washington

The Providence Regional Medical Center Everett

Everett, Washington, United States, 98201

University of Washington

Seattle, Washington, United States, 98195

Northwest Medical Specialties

Tacoma, Washington, United States, 98405

Providence St. Mary Regional Cancer Center

Walla Walla, Washington, United States, 99362

United States, Wisconsin

University of Wisconsin

Madison, Wisconsin, United States, 53792

Argentina

Fundación Investigar

Buenos Aires, Argentina, 1025

CER Instituto Médico Oncología

Florencio Varela, Argentina, B1878DVB

Centro Medico San Roque

San Miguel de Tucuman, Argentina, T4000IAK

Australia, New South Wales

Mater Misericordiae Hospital; Chemotherapy Cottage

Sydney, New South Wales, Australia, 2060

Calvary Mater Newcastle; Medical Oncology

Waratah, New South Wales, Australia, 2298

Australia, Queensland

Wesley Medical Centre; Clinic For Haematology and Oncology

Auchenflower, Queensland, Australia, 4066

Australia, South Australia

Royal Adelaide Hospital; Oncology

Adelaide, South Australia, Australia, 5000

Australia, Victoria

Peter Maccallum Cancer Institute; Medical Oncology

Melbourne, Victoria, Australia, 3000

Austria

Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.

Salzburg, Austria, 5020

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie

Wien, Austria, 1090

Bahamas

Oncology Consultants Limited

Nassau, Bahamas, 09311

Belgium

Cliniques Universitaires St-Luc

Bruxelles, Belgium, 1200

Clinique Ste-Elisabeth

Namur, Belgium, 5000

Sint Augustinus Wilrijk

Wilrijk, Belgium, 2610

Bosnia and Herzegovina

University Clinical Centre of the Republic of Srpska

Banja Luka, Bosnia and Herzegovina, 78000

Clinic of Oncology, University Clinical Center Sarajevo

Sarajevo, Bosnia and Herzegovina, 71000

Brazil

Instituto Nacional do Cancer - INCA

Rio de Janeiro, RJ, Brazil, 20560-120

Liga Norte Riograndense Contra O Câncer

Natal, RN, Brazil, 59040150

Clinica de Oncologia de Porto Alegre - CliniOnco

Porto Alegre, RS, Brazil, 90430-090

Hospital Sao Lucas - PUCRS

Porto Alegre, RS, Brazil, 90610-000

Hospital Nossa Senhora da Conceicao

Porto Alegre, RS, Brazil, 91350-200

Clinica de Neoplasias Litoral

Itajai, SC, Brazil, 88301-220

Instituto do Cancer do Estado de Sao Paulo - ICESP

Sao Paulo, SP, Brazil, 01246-000

Hospital Perola Byington

Sao Paulo, SP, Brazil, 01317-000

Canada, Alberta

Cross Cancer Institute; Clinical Trials

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Ontario

North York General Hospital

Toronto, Ontario, Canada, M2K 1E1

Canada, Quebec

Cuse - Centre Universitaire De Sante; Site Fleurimont

Sherbrooke, Quebec, Canada, J1H 5N4

Canada

CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY

Quebec, Canada, G1S 4L8

Colombia

Clinica del Country

Bogota, Colombia, 11001

Instituto Colombiano Para El Avance De La Medicina: Icamedic

Bucaramanga, Colombia

Centro Medico Imbanaco

Cali, Colombia

Instituto Cancerologico de Nariño

Pasto, Colombia

Czechia

Masarykuv onkologicky ustav

Brno, Czechia, 656 53

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, Czechia, 779 00

Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika

Praha 2, Czechia, 128 08

Fakultni Nemocnice Na Bulovce; Ustav Radiacni Onkologie

Praha, Czechia, 180 00

Denmark

Nordsjællands Hospital, Hillerød, Onkologisk Afdeling

Hillerod, Denmark, 3400

Vejle Sygehus Onkologisk Afd

Vejle, Denmark, 7100

France

HOPITAL JEAN MINJOZ; Oncologie

Besancon, France, 25030

Centre Jean Perrin; Hopital De Jour

Clermont Ferrand, France, 63011

Centre Oscar Lambret; Senologie

Lille, France, 59020

Institut Paoli Calmettes; Oncologie Medicale

Marseille, France, 13273

Institut régional du Cancer Montpellier

Montpellier, France, 34298

Centre D'Oncologie de Gentilly; Oncology

Nancy, France, 54100

Institut Curie; Oncologie Medicale

Paris, France, 75231

Hopital Saint Louis; Service Onco Thoracique

Paris, France, 75475

HOPITAL TENON; Cancerologie Medicale

Paris, France, 75970

Chu La Miletrie; Radiotherapie

Poitiers, France, 86021

Centre Rene Huguenin; ONCOLOGIE GENETIQUE

Saint Cloud, France, 92210

Institut de Cancerologie de La Loire; Radiotherapie

St Priest En Jarez, France, 42271

Germany

Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum

Essen, Germany, 45136

Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie

Halle, Germany, 06120

Facharztzentrum Eppendorf, Studien GbR

Hamburg, Germany, 20249

Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding

Hannover, Germany, 30177

Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

Heidelberg, Germany, 69120

Universitätsklinikum Magdeburg; Frauenheilkunde & Geburtshilfe

Magdeburg, Germany, 39108

Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde

Mainz, Germany, 55131

Mühlenkreiskliniken; Johannes Wesling Klinikum Minden; Klinik für Frauenheilkunde und Geburtshilfe

Minden, Germany, 32429

Rotkreuzklinikum München; Frauenklinik

Muenchen, Germany, 80637

Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie

Trier, Germany, 54290

Greece

Alexandras General Hospital of Athens; Oncology Department

Athens, Greece, 115 28

Univ General Hosp Heraklion; Medical Oncology

Heraklion, Greece, 711 10

University Hospital of Larissa; Oncology

Larissa, Greece, 41 110

Guatemala

Grupo Angeles

Guatemala City, Guatemala, 01015

Centro Oncológico Sixtino / Centro Oncológico SA

Guatemala, Guatemala, 01010

Hungary

Szent Margit Hospital; Dept. of Oncology

Budapest, Hungary, 1032

Semmelweis Egyetem Onkologiai Központ

Budapest, Hungary, 1083

Semmelweis Egyetem Aok; Iii.Sz. Belgyogyaszati Klinika

Budapest, Hungary, 1125

Pécsi Tudományegyetem Áok; Onkoterapias Intezet

Pecs, Hungary, 7623

Italy

Campus Universitario S.Venuta; Centro Oncologico T.Campanella

Catanzaro, Calabria, Italy, 88100

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

Meldola, Emilia-Romagna, Italy, 47014

A.O. Universitaria Policlinico Di Modena; Ematologia

Modena, Emilia-Romagna, Italy, 41100

Arcispedale Santa Maria Nuova; Oncologia

Reggio Emilia, Emilia-Romagna, Italy, 42100

Ospedale Degli Infermi; Divisione Di Oncologia

Rimini, Emilia-Romagna, Italy, 47900

Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia

Udine, Friuli-Venezia Giulia, Italy, 33100

Istituto Europeo Di Oncologia

Milano, Lombardia, Italy, 20141

Fondazione Salvatore Maugeri

Pavia, Lombardia, Italy, 27100

IRCCS Istituto Clinico Humanitas; Oncologia

Rozzano, Lombardia, Italy, 20089

Centro Catanese Di Oncologia; Oncologia Medica

Catania, Sicilia, Italy, 95126

Ospedale Papardo- Piemonte;Oncologia Medica

Messina, Sicilia, Italy, 98158

Ospedale Misericordia E Dolce; Oncologia Medica

Prato, Toscana, Italy, 59100

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica

Perugia, Umbria, Italy, 06156

A.O.U.I. VERONA-OSPEDALE BORGO TRENTO; ONCOLODIA MEDICA-d.O.

Verona, Veneto, Italy, 37126

Japan

Mikawa Breast Cancer Clinic; Breast Surgery

Aichi, Japan, 446-0073

Aichi Cancer Center Hospital, Breast Oncology

Aichi, Japan, 464-8681

Natl Hosp Org Shikoku; Cancer Ctr, Surgery

Ehime, Japan, 791-0280

Kitakyushu Municipal Medical Center; Surgery

Fukuoka, Japan, 802-0077

National Hospital Organization Kyushu Cancer Center;Breast Oncology

Fukuoka, Japan, 811-1395

Gifu University Hospital; Second Department of Surgery

Gifu, Japan, 501-1194

Gunma University Hospital; Department of Breast and Endocrine Surgery

Gunma, Japan, 371-8511

Hiroshima University Hospital; Breast Surgery

Hiroshima, Japan, 734-8551

National Hospital Organization Hokkaido Cancer Center; Breast Surgery

Hokkaido, Japan, 003-0804

Hyogo College Of Medicine; Breast And Endocrine Surgery

Hyogo, Japan, 663-8501

Hyogo Cancer Center; Breast Surgery

Hyogo, Japan, 673-8558

Kanazawa University Hospital; Breast Oncology

Ishikawa, Japan, 920-8641

Iwate Med Univ School of Med; Surgery

Iwate, Japan, 020-8505

Sagara Hospital; Breast Surgery

Kagoshima, Japan, 892-0833

St. Marianna University School of Medicine Hospital, Breast and Endocrine Surgery

Kanagawa, Japan, 216-8511

Tokai University Hospital, Breast and Endocrine Surgery

Kanagawa, Japan, 259-1193

Kumamoto University Hospital; Breast and Endocrine Surgery

Kumamoto, Japan, 860-8556

Kumamoto City Hospital, Breast and Endocrine Surgery

Kumamoto, Japan, 862-8505

Kyoto University Hospital; Breast Surgery

Kyoto, Japan, 606-8507

Tohoku University Hospital; Breast And Endocrine Surgery

Miyagi, Japan, 980-8574

Niigata Cancer Ctr Hospital; Breast Surgery

Niigata, Japan, 951-8566

Okayama University Hospital; Breast, Thyroid Surgery

Okayama, Japan, 700-8558

Kawasaki Medical School Hospital; Breast and Thyroid Surgery

Okayama, Japan, 701-0114

National Hospital Organization Osaka National Hospital; Breast Surgery

Osaka, Japan, 540-0006

Osaka University Hospital; Breast and Endocrine Surgery

Osaka, Japan, 565-0871

Saitama Medical University International Medical Center; Medical Oncology

Saitama, Japan, 350-1298

Saitama Cancer Center, Breast Oncology

Saitama, Japan, 362-0806

Shizuoka Cancer Center; Female Internal Medicine

Shizuoka, Japan, 411-8777

Shizuoka General Hospital; Breast Surgery

Shizuoka, Japan, 420-8527

Jichi Medical University; Breast Oncology

Tochigi, Japan, 329-0498

National Cancer Center Hospital; Breast and Medical Oncology

Tokyo, Japan, 104-0045

Toranomon Hospital; Breast and Endocrine Surgery

Tokyo, Japan, 105-8470

The Cancer Inst. Hosp. of JFCR; Breast Oncology Center

Tokyo, Japan, 135-8550

Showa University Hospital; Breast Surgery

Tokyo, Japan, 142-8666

Tokyo Medical Uni. Hospital; Breast Oncology

Tokyo, Japan, 160-0023

Kyorin University Hospital; Breast Surgery

Tokyo, Japan, 181-8611

Korea, Republic of

Seoul National University Bundang Hospital; Hematology Medical Oncology

Gyeonggi-do, Korea, Republic of, 463-707

Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology

Seoul, Korea, Republic of, 03080

Samsung Medical Centre; Division of Hematology/Oncology

Seoul, Korea, Republic of, 135-710

Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology

Seoul, Korea, Republic of, 138-736

Korea University Guro Hospital; Oncology

Seoul, Korea, Republic of, 152-703

Macedonia, The Former Yugoslav Republic of

Private Health Organization Acibadem Sistina Hospital

Skopje, Macedonia, The Former Yugoslav Republic of, 1000

Malaysia

Beacon International Specialist Centre

Petaling Jaya, Selangor, Selangor, Malaysia, 46050

Pantai Hospital Kuala Lumpur; Dept of Oncology & Radiotherapy

Kuala Lumpur, Malaysia, 59100

Sunway Medical Centre

Selangor, Malaysia, 46150

Mexico

Centro de Investigacion; Clinica Del Pacifico

Acapulco, Mexico, 39670

Centenario Hospital Miguel Hidalgo

Aguascalientes, Mexico, 20230

Núcleo de Especialidades Oncológicas

Guadalajara, Mexico, 44670

Centro Universitario Contra El Cancer

Monterrey, Mexico, 64020

Oaxaca Site Management Organization

Oaxaca, Mexico, 68000

Hospital Privado San Jose; Oncologia

Obregon, Mexico, 85000

Centro Oncológico Estatal; ISSSEMYM Oncología

Toluca, Mexico, 50180

New Zealand

Auckland city hospital; Auckland Regional Cancer Centre and Blood Service

Auckland, New Zealand, 1023

Waikato Hospital; Regional Cancer Center

Hamilton, New Zealand

Panama

Centro Hemato Oncologico Paitilla

Panama City, Panama, 083200752

Peru

Hospital Nacional Carlos Alberto Seguin Escobedo-Essalud; Oncology & Haemathology

Arequipa, Peru, 04001

Hospital Nacional Edgardo Rebagliati Martins; Oncologia

Lima, Peru, 11

Unidad de Investigacion Oncologia Clinica - Piura; Unidad de Oncología Clínica

Piura, Peru, 20011

Philippines

Cebu Cancer Institute; Perpetual Succour Hospital

Cebu, Philippines, 6000

Cardinal Santos Medical Center

San Juan, Philippines, 1502

Poland

Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii

Bydgoszcz, Poland, 85-796

Medical University of Gdansk

Gdansk, Poland, 80-211

Centrum Onkologii, Instytut, Klinika Chemioterapii; Oddzial Chemoterapii

Krakow, Poland, 31-115

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, Poland, 20-090

Cent.Onkologii-Instytut im. M. S-Curie, Klinika Now. Piersi i Chirurgii Rekon

Warszawa, Poland, 02-781

Portugal

IPO do Porto; Servico de Oncologia Medica

Porto, Portugal, 4200-072

Romania

Coltea Hospital; Oncology

Bucharest, Romania

Prof. Dr. I. Chiricuta Institute of Oncology

Cluj Napoca, Romania, 400015

Cluj Clinical County Hospital; Oncology Dept

Cluj-Napoca, Romania, 400006

Russian Federation

Ivanovo Regional Oncology Dispensary

Ivanovo, Russian Federation, 153040

Clinical Oncology Dispensary of Ministry of Health of Tatarstan

Kazan, Russian Federation, 420029

Blokhin Cancer Research Center; Combined Treatment

Moscow, Russian Federation, 115478

Moscow city oncology hospital #62 of Moscow Healthcare Department

Moscow, Russian Federation, 143423

State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary

Pyatigorsk, Russian Federation, 357502

Ryazan State Medical University Named after I.P.Pavlov

Ryazan, Russian Federation, 390011

SBI of Healthcare Samara Regional Clinical Oncology Dispensary

Samara, Russian Federation, 443031

SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary

Stavropol, Russian Federation, 355045

Tula Regional Oncology Dispensary

Tula, Russian Federation, 300053

GUZ Vladimir Regional Clinical Oncological Dispensary

Vladimir, Russian Federation, 600009

Spain

Hospital General Universitario de Elche; Servicio de Oncologia

Elche, Alicante, Spain, 03203

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, Spain, 15706

Hospital del Mar; Servicio de Oncologia

Barcelona, Spain, 08003

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, Spain, 08035

Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia

Jaen, Spain, 23007

Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología

La Coruña, Spain, 15006

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, Spain, 28007

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, Spain, 28041

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, Spain, 28046

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Malaga, Spain, 29010

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, Spain, 46010

Sweden

Uni Hospital Linkoeping; Dept. of Oncology

Linköping, Sweden, 58185

Skånes Universitetssjukhus; Kliniska Forskningsenheten Onkologimottagning medicinsk behandling

Malmö, Sweden, 205 02

Switzerland

Kantonsspital Baden; Medizinische Klinik, Onkologie

Baden, Switzerland, 5404

Universitaetsspital Basel; Onkologie

Basel, Switzerland, 4031

Kantonsspital Graubünden;Onkologie und Hämatologie

Chur, Switzerland, 7000

Taiwan

Changhua Christian Hospital; Hematology-Oncology

Changhua, Taiwan, 500

Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery

Kaohsiung, Taiwan, 807

National Taiwan Uni Hospital; Dept of Oncology

Taipei, Taiwan, 100

Tri-Service General Hospital; Hematology and Oncology

Taipei, Taiwan, 114

Thailand

National Cancer Inst.

Bangkok, Thailand, 10400

Rajavithi Hospital; Division of Medical Oncology

Bangkok, Thailand, 10400

Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc

Bangkok, Thailand, 10400

Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology

Bangkok, Thailand, 10700

Maharaj Nakorn Hospital; Internal Medicine

Chiang Mai, Thailand, 50200

Prince of Songkla Uni ; Unit of Medical Oncology

Songkhla, Thailand, 90110

Turkey

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology

Adana, Turkey, 01250

Cukurova Uni Faculty of Medicine; Medical Oncology

Adana, Turkey, 01330

Gazi Uni Medical Faculty Hospital; Oncology Dept

Ankara, Turkey, 06500

Ege Uni Medical Faculty Hospital; Oncology Dept

Izmir, Turkey, 35100

United Kingdom

Bristol Haematology and Oncology Centre

Bristol, United Kingdom, BS2 8ED

Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom, CB2 0QQ

The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit

Glasgow, United Kingdom, G12 0YN

Leicester Royal Infirmary; Dept. of Medical Oncology

Leicester, United Kingdom, LE1 5WW

Royal Free Hospital; Dept of Oncology

London, United Kingdom, NW3 2QG

Guys Hospital; Management Offices

London, United Kingdom, SE1 9RT

Royal Marsden Hospital; Dept of Med-Onc

London, United Kingdom, SW3 6JJ

Christie Hospital; Breast Cancer Research Office

Manchester, United Kingdom, M20 4QL

Nottingham City Hospital; Oncology

Nottingham, United Kingdom, NG5 1PB

Peterborough City Hospital; Oncology Ward

Peterborough, United Kingdom, PE 3 9GZ

Queen Alexandra Hospital, Portsmouth

Portsmouth, United Kingdom, PO6 3LY

Weston Park Hospital; Cancer Clinical Trials Centre

Sheffield, United Kingdom, S10 2SJ

Southampton General Hospital; Somers Cancer Research Building

Southampton, United Kingdom, SO16 6YD

Uni Hospital of North Staffordshire; Staffordshire Oncology Centre

Stoke-on-Trent, United Kingdom, ST4 6QG

Royal Marsden Hospital; Dept of Medical Oncology

Sutton, United Kingdom, SM2 5PT

Royal Cornwall Hospital; Dept of Clinical Oncology

Truro, United Kingdom, TR1 3LJ

Sponsors and Collaborators

Hoffmann-La Roche

Genentech, Inc.

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Perez EA, de Haas SL, Eiermann W, Barrios CH, Toi M, Im YH, Conte PF, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Stanzel S, Patre M, Ellis PA. Relationship between tumor biomarkers and efficacy in MARIANNE, a phase III study of trastuzumab emtansine +/- pertuzumab versus trastuzumab plus taxane in HER2-positive advanced breast cancer. BMC Cancer. 2019 May 30;19(1):517. doi: 10.1186/s12885-019-5687-0. Erratum In: BMC Cancer. 2019 Jun 24;19(1):620.

Bighin C, Pronzato P, Del Mastro L. Trastuzumab emtansine in the treatment of HER-2-positive metastatic breast cancer patients. Future Oncol. 2013 Jul;9(7):955-7. doi: 10.2217/fon.13.74.

Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012 Mar 22;12(4):278-87. doi: 10.1038/nrc3236.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01120184
• Other Study ID Numbers: BO22589; 2009-017905-13 ( EudraCT Number )
• First Posted: May 10, 2010
• Results First Posted: February 23, 2017
• Last Update Posted: November 7, 2017
• Last Verified: November 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Maytansine; Docetaxel; Ado-Trastuzumab Emtansine; Trastuzumab; Pertuzumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Immunotoxins; Immunoconjugates; Immunologic Factors; Physiological Effects of Drugs