Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer

作者：José Baselga, Mario Campone, Martine Piccart, Howard A. Burris, Hope S. Rugo, Tarek Sahmoud, Shinzaburo Noguchi, Michael Gnant, Kathleen I. Pritchard, Fabienne Lebrun, J. Thaddeus Beck, Yoshinori Ito, Denise A. Yardley, Ines Deleu, Alejandra Perez, Thomas Bachelot, Luc Vittori, Zhiying Xu, Pabak Mukhopadhyay, David Lebwohl, Gabriel N. Hortobágyi · 发表于：New England Journal of Medicine · 年份：2011 · DOI：10.1056/nejmoa1109653 · 被引用次数：2858 · 研究领域：PI3K/AKT/mTOR signaling in cancer、Advanced Breast Cancer Therapies、Male Breast Health Studies

BACKGROUND: Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway. In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity. METHODS: In this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). The primary end point was progression-free survival. Secondary end points included survival, response rate, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed. RESULTS: Baseline characteristics were well balanced between the two study groups. The median age was 62 years, 56% had visceral involvement, and 84% had hormone-sensitive disease. Previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. ...