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.
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 (ClinicalTrials.gov 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.
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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.
- 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]