Final TH3RESA, EMILIA Results Confirm Role of Trastuzumab Emtansine in HER2+ Breast Cancer

Final results from two large phase III trials confirm that the drug-antibody conjugate trastuzumab emtansine improves overall survival (OS) over other treatment options in patients with previously treated HER2-positive metastatic breast cancer. The results of the EMILIA and TH3RESA trials confirm the agent’s role in this setting.

Trastuzumab emtansine, which links the antibody trastuzumab with the cytotoxic microtubule inhibitor DM1, was approved based on earlier results of the EMILIA study. The new analysis of that trial offers approximately twice the length of follow-up, at a median of 24.1 months.

Led by Véronique Diéras, MD, of Institut Curie Paris & Saint Cloud in Paris, the EMILIA trial enrolled 991 patients with previously treated advanced HER2-positive breast cancer between 2009 and 2011; they were randomized to receive trastuzumab emtansine (495 patients) or capecitabine plus lapatinib (control group; 496 patients). The study protocol was amended in 2012 to allow treatment crossover to the trastuzumab group. Results of this final analysis of EMILIA, and that of the TH3RESA trial, were published in Lancet Oncology.

In the EMILIA trial, the trastuzumab emtansine group had a median OS of 29.9 months, compared with 25.9 months in the capecitabine plus lapatinib group, for a hazard ratio (HR) of 0.75 (95% CI, 0.64–0.88). A total of 136 control group patients (27%) eventually crossed over to receive trastuzumab emtansine. The safety profile was similar to that seen in previous reports, with thrombocytopenia, increased aspartate aminotransferase levels, and anemia being the most common grade 3 or higher adverse events in the trastuzumab emtansine patients.

The TH3RESA trial included 602 patients, randomized to the antibody-drug conjugate or to physician’s choice. In this case, the final median follow-up period was 30.5 months, and again, the OS was better with trastuzumab emtansine. The median OS was 22.7 months compared with 15.8 months with physician’s choice, for an HR of 0.68 (95% CI, 0.54–0.85; P = .0007). Serious adverse events were reported in 25% of trastuzumab emtansine patients and in 22% of physician’s choice patients.

“Trastuzumab emtansine offers patients with previously treated HER2-positive metastatic breast cancer an effective therapeutic option with an acceptable safety profile, without the need for conventional systemic chemotherapy,” wrote authors led by Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute in Boston.

EMILIA investigators agreed, concluding that alongside the TH3RESA results, “the EMILIA study data reaffirm that trastuzumab emtansine is an efficacious and tolerable treatment for patients with previously treated HER2-positive metastatic breast cancer.”