Phase 3
Completed N=1,095
A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)
Source: ClinicalTrials.gov NCT01120184 ↗Enrolled (actual)
1,095
Serious AEs
24.1%
Results posted
Feb 2017
Primary outcomePrimary: Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment — 63.3; 64.3; 59.8 percentage of participants
◆ Published Evidence
Highly cited
2,143citations · ~153 / year
Antibody therapy of cancer.
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.
Linked Publications (3)
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Antibody therapy of cancer.
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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.
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Trastuzumab emtansine in the treatment of HER-2-positive metastatic breast cancer patients.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment |
63.3; 64.3; 59.8 | — |
| PRIMARY Progression-Free Survival (PFS) According to IRF Assessment |
13.7; 14.1; 15.2 | 0.3125 |
| SECONDARY Percentage of Participants Who Died Prior to Clinical Cutoff |
46.3; 47.7; 46.3 | — |
| SECONDARY Overall Survival (OS) at Clinical Cutoff |
50.86; 53.68; 51.78 | 0.6568 |
| SECONDARY Percentage of Participants With Death or Disease Progression According to Investigator Assessment |
72.1; 70.3; 67.5 | — |
| SECONDARY PFS According to Investigator Assessment |
12.5; 14.1; 14.8 | — |
| SECONDARY Percentage of Participants Experiencing Treatment Failure |
85.8; 82.6; 80.2 | — |
| SECONDARY Time to Treatment Failure (TTF) |
10.2; 12.1; 11.8 | — |
| SECONDARY One-Year Survival Rate |
91.4; 92.4; 91.9 | — |
| SECONDARY Percentage of Participants With Grade ≥3 Adverse Events |
54.1; 45.4; 46.2 | — |
| SECONDARY Percentage of Participants Who Died at 2 Years |
20.3; 20.2; 19.6 | — |
| SECONDARY Overall Survival Truncated at 2 Years |
79.7; 79.8; 80.4 | — |
| SECONDARY Percentage of Participants With Grade 5 Adverse Events |
1.7; 1.1; 1.9 | — |
| SECONDARY Percentage of Participants With Grade 3-4 Laboratory Parameters |
4.3; 5.8; 6.9; 20.2; 5.5; 5.0 | — |
| SECONDARY Percentage of Participants With Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status |
7.6; 6.1; 7.9 | — |
| SECONDARY Hospitalization Days |
6; 5; 8 | — |
| SECONDARY Percentage of Participants With Hospitalization |
21.8; 20.2; 22.1 | — |
| SECONDARY Percentage of Participants With Objective Response According to IRF Assessment |
67.9; 59.7; 64.2 | — |
| SECONDARY Percentage of Participants With Objective Response According to Investigator Assessment |
69.3; 64.6; 67.5 | — |
| SECONDARY Duration of Response According to IRF Assessment |
12.5; 20.7; 21.2 | — |
| SECONDARY Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) According to IRF Assessment |
— | — |
| SECONDARY 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 |
93.1; 60.8; 68.8 | — |
| SECONDARY Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module |
22.3; 14.5; 21.3; 38.0; 36.0; 52.6 | — |
| SECONDARY Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module |
15.0; 7.6; 11.8; 34.7; 17.9; 34.7 | — |
| SECONDARY 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 |
61.8; 50.9; 50.6 | — |
| SECONDARY Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score |
3.6; 7.7; 9.0 | — |
| SECONDARY Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score |
85.0; 85.5; 85.7; -1.6; 2.3; -0.2 | — |
| SECONDARY Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score |
15.3; 9.5; 13.6; 0.4; -0.0; -4.3 | — |
| SECONDARY Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score |
32.9; 33.6; 32.7; 4.5; -5.3; -3.7 | — |
| SECONDARY 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 |
75.0; 66.9; 63.9 | — |
| SECONDARY Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels |
61.9; 51.7; 66.1 | — |
| SECONDARY Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels |
59.4; 57.6; 56.1 | — |
| SECONDARY PFS According to IRF Assessment Among Those With High HER2 mRNA Levels |
15.9; 18.6; 18.7 | — |
| SECONDARY Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels |
66.5; 70.1; 62.4 | — |
| SECONDARY PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels |
12.4; 10.2; 14.5 | — |
| SECONDARY Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels |
38.8; 41.2; 45.1 | — |
| SECONDARY OS at Clinical Cutoff Among Those With High HER2 mRNA Levels |
NA; 65.97; 55.39 | — |
| SECONDARY Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels |
51.8; 52.9; 45.2 | — |
| SECONDARY OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels |
43.96; 47.84; 53.29 | — |
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT01120184) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.