Trastuzumab Emtansine Is Directly Compared with Trastuzumab Plus Docetaxel

The combination of trastuzumab, a monoclonal antibody that targets HER2, and taxane-based chemotherapy has been shown to significantly improve overall survival (OS) and progression-free survival (PFS) in patients with HER2-positive breast cancers compared with chemotherapy alone. However, chemotherapy frequently causes adverse events that can require treatment discontinuation and negatively affect quality of life. Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate in which trastuzumab is stably linked to DM1, a cytotoxic microtubule inhibitor. T-DM1 is expected to have a favorable safety profile compared with conventional chemotherapy because the cytotoxic agent is delivered directly to HER2-overexpressing cancer cells, but this hypothesis has not been formally tested. Hurvitz and colleagues conducted a multicenter, open-label, phase II trial in which patients with advanced or metastatic HER2-positive breast cancer were randomized to receive either T-DM1 or trastuzumab plus docetaxel. The primary endpoints were PFS and safety, and secondary endpoints included OS, objective response rate, and quality of life. T-DM1 significantly improved PFS compared with trastuzumab plus docetaxel (14.2 months vs. 9.2 months), although the objective response rate and preliminary OS were similar in both arms of the study. Importantly, only 46.4% of the T-DM1 group experienced grade 3 or higher adverse events compared with 90.9% of the trastuzumab plus docetaxel group, and adverse events leading to treatment discontinuation occurred in only 7.2% of the T-DM1 group compared with 40.9% of the trastuzumab plus docetaxel group. Furthermore, quality of life scores were significantly higher in the T-DM1 group. These results, which await validation in an ongoing phase III study, indicate that targeted delivery of cytotoxic chemotherapy by T-DM1 may be safer and more effective in patients with HER2-positive breast cancer than trastuzumab plus standard chemotherapy.

Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, et al. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer. J Clin Oncol 2013 Feb 4 [Epub ahead of print].