Phase 3 Study Update of Trastuzumab Emtansine for Metastatic HER2-positive Breast CancerXeloda; Roche) and lapatinib (Tykerb; GlaxoSmithKline) in those previously treated with trastuzumab (Herceptin; Genentech) and a taxane, according to a study published in the New England Journal of Medicine online October 1 to coincide with a presentation at the European Society for Medical Oncology (ESMO) in Vienna, Austria.
Results from the Phase 3 EMILIA trial showed median PFS was 9.6 months in the T-DM1 arm vs 6.4 months in the lapatinib plus capecitabine arm (HR 0.65; 95% CI, 0.55–0.77; P<0.001) among the 991 patients treated, reported Sunil Verma, MD, of Toronto, CA, for the EMILIA Study Group.
Two interim OS analyses were planned. The first found OS was not reached in the T-DM1 arm vs a median of 23.3 months in the lapatinib plus capecitabine arm (HR 0.621; 95% CI 0.475–0.813; P=0.0005). Median OS at the second interim analysis crossed the stopping boundary for efficacy (30.9 months vs. 25.1 months; HR 0.68; 95% CI, 0.55–0.85; P<0.001).
Updated OS results also reported at ESMO by Dr. Verma showed that a 1-year, median OS was 84.7% in the T-DM1 arm vs. 77% in the lapatinib plus capecitabine arm; at 2 years, it was 65.4% and 46.5%, respectively.
Objective response was significantly higher in the T-DM1 arm, 43.6%, vs. 30.8% in the lapatinib plus capecitabine arm (P<0.001). Results for other secondary end points, including clinical benefit rate and time to treatment failure, favored T-DM1, he reported.
Higher rates of Grade 3 or 4 adverse events were reported in the lapatinib plus capecitabine arm, 57%, vs. 41% in the T-DM1 arm. Thrombocytopenia and increased serum aminotransferase levels occurred more frequently with T-DM1; in the lapatinib plus capecitabine arm, incidence of diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were higher.
“…Our study shows that T-DM1 has therapeutic potential, across a heterogeneous population of patients, for the treatment of advanced, HER2-positive breast cancer that has progressed during or after treatment with trastuzumab and a taxane,” Dr. Verma concluded.
The study was funded by F. Hoffmann-La Roche/Genentech.