Ado-trastuzumab emtansine in combination with docetaxel with or without pertuzumab appeared efficacious in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic locally advanced or metastatic breast cancer, a study published in the journal Annals of Oncology has shown.1
Because preclinical trials demonstrated enhanced antitumor activity when ado-trastuzumab emtansine was combined with docetaxel or pertuzumab, researchers sought to assess the feasibility of ado-trastuzumab emtanasine plus docetaxel in patients with HER2-positive metastatic breast cancer and with or without pertuzumab for those with locally advanced breast cancer.
For the phase 1b/2a study, researchers enrolled 25 patients with metastatic breast cancer and 73 patients with locally advanced disease. Patients with metastatic breast cancer received ado-trastuzumab emtansine 3.6 mg/kg plus docetaxel 60 mg/m2.
Participants with locally advanced breast cancer received ado-trastuzumab emtansine 3.6 mg/kg with docetaxel 100 mg/m2 and granulocyte-colony stimulating factor (G-CSF), or plus docetaxel 75 mg/m2 and pertuzumab 420 mg (840 mg for cycle 1) with G-CSF support.
Results showed that the objective response rate was 80.0% (95% CI, 59.3 – 93.2) and median progression-free survival was 13.8 months in patients with metastatic breast cancer. In locally advanced disease, the pathologic complete response rate was 60.3% (95% CI, 48.1 – 71.5).
In terms of safety, 72% and 29% of patients with metastatic and locally advanced breast cancer, respectively, experienced grade 3 or 4 neutropenia. Nearly half of all patients required dose adjustments due to treatment-related toxicities.
Ado-trastuzumab emtansine is an antibody-drug conjugate consisting of trastuzumab, a monoclonal antibody frequently used for HER2-positive cancers, linked with DM1, a cytotoxic agent. It is indicated as a single-agent for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane.
- Martin M, Fumoleau P, Dewar JA, et al. Trastuzumab emtansine (T-DM1) plus docetaxel with or without pertuzumab in patients with HER2-positive locally advanced or metastatic breast cancer: results from a phase Ib/IIa study [published online ahead of print April 6, 2016]. Ann Oncol. doi: 10.1093/annonc/mdw157.