Study demonstrates that T-DM1, a new antibody-drug conjugate, significantly prolongs progression-free survival and overall survival in patients with metastatic HER2-positive breast cancer. The European Society of Medical Oncology conference reported: Final data from the highly anticipated EMILIA trial, which examined the clinical efficacy of T-DM1 in patients with metastatic breast cancer compared to conventional therapy – Tykerb/Capecitabine (Xeloda). The patients tested were those who had failed treatment with paclitaxel and trastuzumab. The results of the study were also published online in the New England Journal of Medicine; the first author of the article is Dr. Sunil Verma of the Sunnybrook Odette Cancer Centre in Toronto, Lake Ontario. The trial used median progression-free survival and overall survival as co-efficacy endpoints, and the results of the randomized trial in 991 subjects were as follows: progression-free survival: 9.6 months in the T-DM1 group and only 6.4 months in the capecitabine/lapatinib group. Overall survival: 30.9 months in the T-DM1 group and only 25.1 months in the capecitabine/lapatinib group. The hazard ratio for disease progression or death from any cause in the T-DM1 group was 0.65 (95% CI 0.55 – 0.77) relative to the capecitabine/lapatinib group; all-cause mortality was 0.68 (95% CI 0.55 – 0.85). Results of the interim analysis were presented at the annual meeting of the American Society of Clinical Oncology in June; the time difference in progression-free survival met the researchers’ expected criteria and was significantly superior; however, the time difference in overall survival was not. Verma and his colleagues stated that the overall survival gap was consistent with the efficacy endpoint as more and more events accumulated at follow-up. All secondary findings also favored the T-DM1 group; these included: a 5-point reduction in objective response rate, mean time to onset of action, and a 5-point reduction in the functional assessment outcome index of the breast cancer trial. Notably, the objective response rate in the T-DM1 group was 43.6% vs. 30.8% in the capecitabine/lapatinib group (P<0.001); mean time to onset of action was 12.6 months vs. 6.5 months, respectively. The rate of 3-4 and adverse events in the T-DM1 group was 41% vs. 57% in the capecitabine/lapatinib group, according to the researchers. However, the T-DM1 group was more likely to have adverse events such as thrombocytopenia and elevated liver enzymes. Nausea, vomiting, diarrhea and hand-foot syndrome were more frequent in the capecitabine/lapatinib group. t-DM1 uses the drug trastuzumab site to target cancer cells carrying human epidermal growth factor receptor 2 (HER2). After the drug fuses with cancer cells, it releases cytotoxic trastuzumab sites that kill the cancer cells. In the NEJM report, Verma and colleagues said it was clear that "T-DM1 is not a panacea" based on the Kaplan-Meier curve of progression or death. After 27 months of follow-up, only 17% of the T-DM1 group had survived without progression; nevertheless, the T-DM1 group outperformed the capecitabine/lapatinib group (7% of survivors and no progression for 27 months). At 34 months of follow-up after trial initiation, the overall patient survival rate was approximately 45%. Overall survival was substantially better after 30 months of treatment with T-DM1, according to the Kaplan-Meier curve in the NEJM report. In the journal article, the researchers write, "The stable and favorable trial data for T-DM1 in the primary and secondary endpoints of this trial suggest that the new antibody-drug conjugate T-DM1 is effective in treating HER2-positive advanced breast cancer." They add that the lower rate of serious adverse events just confirms that cytotoxic drugs targeting intercellular delivery to HER2 overexpressing cells improve the therapeutic index of the drug by reducing contact with normal tissue cells. In addition, Verma and his colleagues note that the better side effect profile of T-DM1 means that more patients can maintain an effective dose of the drug and "exert sustained efficacy."