Final Overall Survival Results of EMILIA Trial in Breast Cancer
As reported in The Lancet Oncology by Diéras et al, the final overall survival results of the phase III EMILIA trial show improved outcome with ado-trastuzumab emtansine (Kadcyla) vs capecitabine plus lapatinib (Tykerb) in previously treated HER2-positive advanced breast cancer. Approval of trastuzumab emtansine for treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab (Herceptin) and a taxane is based on progression-free survival and interim overall survival findings in the trial.
Study Details
In the trial, 991 patients previously treated with trastuzumab and a taxane were randomized between February 2009 and October 2011 to receive ado-trastuzumab emtansine at 3.6 mg/kg every 3 weeks (n = 495) or oral capecitabine at 1,000 mg/m² twice daily on days 1 to 14 of each 21-day cycle plus lapatinib at 1,250 mg orally once daily on days 1 to 21 (n = 496). In May 2012, the study protocol was amended to allow crossover from control to ado-trastuzumab emtansine after the second interim overall survival analysis crossed the prespecified efficacy boundary.
Overall Survival
The cutoff date for the final analysis was in December 2014. The median duration of follow-up was 47.8 months in the ado-trastuzumab emtansine group and 41.9 months in the control group. Median overall survival was 29.9 months (95% confidence interval [CI] = 26.3–34.1 months) in the ado-trastuzumab emtansine group vs 25.9 months (95% CI = 22.7–28.3 months) in the control group (hazard ratio = 0.75, 95% CI = 0.64–0.88).
In the control group, 136 patients (27%) crossed over to ado-trastuzumab emtansine after the second interim overall survival analysis (median follow-up duration = 24.1 months). In the ado-trastuzumab emtansine group, 254 patients (51%) received capecitabine and 241 patients (49%) received lapatinib (separately or in combination) after ado-trastuzumab emtansine discontinuation. A post hoc sensitivity analysis that censored patients at the time of crossover to ado-trastuzumab emtansine showed similar outcome (median = 29.9 vs 24.6 months, HR = 0.69, 95% CI = 0.59–0.82).
Adverse Events
Grade ≥ 3 adverse events occurred in 48% of the ado-trastuzumab emtansine group vs 60% of the control group. The most common events were thrombocytopenia (14%), increased aspartate transaminase (5%), and anemia (4%) in the ado-trastuzumab emtansine group and diarrhea (21%), palmar-plantar erythrodysesthesia syndrome (18%), and vomiting (5%) in the control group. Three deaths in the ado-trastuzumab emtansine group (due to metabolic encephalopathy, neutropenic sepsis, and acute myeloid leukemia) and two deaths in the control group (due to coronary artery disease and multiorgan failure) were considered related to study treatment.
The investigators concluded: “This descriptive analysis of final overall survival in the EMILIA trial shows that trastuzumab emtansine improved overall survival in patients with previously treated HER2-positive metastatic breast cancer even in the presence of crossover treatment. The safety profile was similar to that reported in previous analyses, reaffirming trastuzumab emtansine as an efficacious and tolerable treatment in this patient population.”
The study was funded by F. Hoffmann-La Roche/Genentech.
Véronique Diéras, MD, of Institut Curie, Paris, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
