Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer

作者：Sunil Verma, David Miles, Luca Gianni, Ian E. Krop, Manfred Welslau, José Baselga, Mark D. Pegram, Do‐Youn Oh, Véronique Dièras, Ellie Guardino, Fang Ting Liang, Michael W. Lu, Steven R. Olsen, Kim T. Blackwell · 发表于：New England Journal of Medicine · 年份：2012 · DOI：10.1056/nejmoa1209124 · 被引用次数：3839 · 研究领域：HER2/EGFR in Cancer Research、Breast Cancer Treatment Studies、Cancer Treatment and Pharmacology

BACKGROUND: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker. METHODS: We randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane, to T-DM1 or lapatinib plus capecitabine. The primary end points were progression-free survival (as assessed by independent review), overall survival, and safety. Secondary end points included progression-free survival (investigator-assessed), the objective response rate, and the time to symptom progression. Two interim analyses of overall survival were conducted. RESULTS: Among 991 randomly assigned patients, median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001), and median overall survival at the second interim analysis crossed the stopping boundary for efficacy (30.9 months vs. 25.1 months; hazard ratio for death from any cause, 0.68; 95% CI, 0.55 to 0.85; P<0.001). The objective response rate was higher with T-DM1 (43.6%, vs. 30.8% with lapatinib plus capecitabine; P<0.001); results for all additional se...