In addition to non-inferiority to trastuzumab plus a taxane, first-line treatment with trastuzumab emtansine demonstrated better tolerability among women with human epidermal growth factor receptor 2 (HER2)-positive, advanced breast cancer, according to a study published in the Journal of Clinical Oncology.1

Trastuzumab and pertuzumab are monoclonal antibodies that target HER2 and are approved for treatment of HER2-positive breast cancers. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate indicated for advanced HER2-positive breast cancer, combines the properties of trastuzumab with the cytotoxic activity of DM1.

A phase 2 study previously demonstrated the efficacy and safety of T-DM1 in treatment-naive patients with HER2-positive, metastatic breast cancer, and the combination of T-DM1 and pertuzumab was shown to have synergistic activity in a phase 1b and 2 study.

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Researchers evaluated the efficacy and safety of trastuzumab emtansine with or without pertuzumab compared with trastuzumab plus a taxane among previously untreated patients with HER2-positive, advanced breast cancer.

For the phase 3 MARIANNE study ( Identifier: NCT01120184), researchers enrolled 1095 women who had received no prior therapy for advanced disease. Participants were randomly assigned 1:1:1 to trastuzumab plus a taxane, T-DM1 plus placebo, or T-DM1 plus pertuzumab.

Median progression-free survival was 13.7 months with trastuzumab plus a taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab, suggesting that T-DM1 and T-DM1 plus pertuzumab were non-inferior for progression-free survival to trastuzumab plus a taxane. Neither T-DM1 arm was superior to trastuzumab plus a taxane.

The researchers also found that 67.9% of patients who received trastuzumab plus a taxane achieved an objective response, vs 59.7% for T-DM1, and 64.2% for T-DM1 plus pertuzumab; median duration of response was 12.5 months, 20.7 months, and 21.2 months, respectively.

RELATED: FCGR3A-158 Polymorphism Predictive of Trastuzumab Efficacy in Breast Cancer

A smaller number of patients in the T-DM1 arms experienced grade 3 or worse adverse events and discontinued treatment due to adverse events compared with those in the trastuzumab-taxane arm. Patients in the T-DM1 arms maintained a relatively high health-related quality of life for a longer period.


  1. Perez EA, Barrios C, Eiermann W, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2–positive, advanced breast cancer: Primary results from the phase III MARIANNE Study. J Clin Oncol. 2016 Nov 7. doi: 10.1200/JCO.2016.67.4887 [Epub ahead of print]