Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study

作者：Kimberly Blackwell, Harold J. Burstein, Anna Maria Storniolo, Hope S. Rugo, George W. Sledge, Gursel Aktan, Catherine Elizabeth Ellis, Allison M. Florance, Svetislava J. Vukelja, Joachim Bischoff, José Baselga, Joyce O’Shaughnessy · 发表于：Journal of Clinical Oncology · 年份：2012 · DOI：10.1200/jco.2011.35.6725 · 被引用次数：553 · 研究领域：HER2/EGFR in Cancer Research、Advanced Breast Cancer Therapies、Cancer Treatment and Pharmacology

PURPOSE: Phase III EGF104900 data demonstrated that lapatinib plus trastuzumab significantly improved progression-free survival (PFS) and clinical benefit rate versus lapatinib monotherapy, offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). Final planned overall survival (OS) analysis from EGF104900 is reported here. PATIENTS AND METHODS: Patients with HER2-positive MBC whose disease progressed during prior trastuzumab-based therapies were randomly assigned to receive lapatinib monotherapy or lapatinib in combination with trastuzumab. OS and updated PFS data are presented using Kaplan-Meier curves and log-rank tests stratified for hormone receptor and visceral disease status. Subgroup analyses were conducted to identify characteristics of patients deriving the greatest clinical benefit. RESULTS: In this updated final analysis of all patients randomly assigned with strata (n = 291), lapatinib plus trastuzumab continued to show superiority to lapatinib monotherapy in PFS (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .011) and offered significant OS benefit (HR, 0.74; 95% CI, 0.57 to 0.97; P = .026). Improvements in absolute OS rates were 10% at 6 months and 15% at 12 months in the combination arm compared with the monotherapy arm. Multiple baseline factors, including Eastern Cooperative Oncology Group performance status of 0, nonvisceral disease, < three metasta...