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依维莫司治疗绝经后激素受体阳性的晚期乳腺癌
Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer


José Baselga ... 肿瘤 • 2012.02.09
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摘要


背景

乳腺癌内分泌治疗的抗药性与哺乳动物雷帕霉素靶(mTOR)细胞内信号通路激活有关。此前有研究显示mTOR抑制剂Everolimus与内分泌疗法联用时显示出抗肿瘤活性。


方法

在这项三期随机试验中,我们在724名激素受体阳性乳腺癌患者(过去均接受过非甾体芳香酶辅助治疗,或治疗晚期疾病[或同时有这两项治疗]时,发生了复发或进展)中,比较了依维莫司加依西美坦和依西美坦加安慰剂这两种疗法(以2:1的比例随机分配)。主要终点是无进展生存时间。次要终点包括生存时间、治疗有效率和安全性。独立的数据和安全监测委员会在出现359次无进展生存事件后进行事先计划的中期分析。


结果

两组患者的基线特征十分平衡。中位年龄为62岁,56%有脏器受累,84%有对激素敏感的疾病。以往的治疗包括来曲唑或阿那曲唑(100%),他莫昔芬(48%),氟维司群(16%)和化疗(68%)。最常见的3级或者4级不良事件为口炎(依维莫司加依西美坦组和安慰剂加依西美坦组分别为8%和1%)、贫血(6%和<1%)、呼吸困难(4%和1%)、高血糖(4%和<1%)、疲乏(4%和1%)、肺炎(3%和0%)。在中期分析时,据地方研究者的估算,中位无进展生存期依维莫司加依西美坦组为6.9个月,依西美坦加安慰剂组2.8个月(病情进展或死亡的风险比为0.43;95%可信区间[CI],0.35到0.54;P<0.001)。按照中心研究者的评估,中位无进展生存期分别为10.6个月和4.1个月(风险比,0.36;95% CI,0.27~0.47;P<0.001)。


结论

对于激素受体阳性晚期乳腺癌并曾经接受过非甾体芳香酶抑制剂治疗的患者,依维莫司加一种芳香酶抑制剂延长了他们的无进展生存期(诺华公司(Novartis)资助;BOLERO-2在ClinicalTrials.gov注册号为NCT 00863655)。





作者信息

José Baselga, M.D., Ph.D., Mario Campone, M.D., Ph.D., Martine Piccart, M.D., Ph.D., Howard A. Burris, III, M.D., Hope S. Rugo, M.D., Tarek Sahmoud, M.D., Ph.D., Shinzaburo Noguchi, M.D., Michael Gnant, M.D., Kathleen I. Pritchard, M.D., Fabienne Lebrun, M.D., J. Thaddeus Beck, M.D., Yoshinori Ito, M.D., Denise Yardley, M.D., Ines Deleu, M.D., Alejandra Perez, M.D., Thomas Bachelot, M.D., Ph.D., Luc Vittori, M.Sc., Zhiying Xu, Ph.D., Pabak Mukhopadhyay, Ph.D., David Lebwohl, M.D., and Gabriel N. Hortobagyi, M.D. From Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston (J.B.); Institut de Cancérologie de l'Ouest/René Gauducheau, Nantes Saint Herblain, France (M.C.); Institute Jules Bordet, Brussels (M.P., F.L.); Sarah Cannon Research Institute, Nashville (H.A.B., D.Y.); University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.); Novartis, East Hanover, NJ (T.S., Z.X., P.M., D.L.); Osaka University, Department of Breast and Endocrine Surgery, Osaka, Japan (S.N.); the Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna (M.G.); Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto (K.I.P.); Highlands Oncology Group, Fayetteville, AR (J.T.B.); Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake, Tokyo (Y.I.); Oncology Center, AZ Nikolass, Sint-Niklaas, Belgium (I.D.); Memorial Cancer Institute, Hollywood, FL (A.P.); Centre Léon-Bérard, Lyon, France (T.B.); Novartis Pharma, Basel, Switzerland (L.V.); and the University of Texas M.D. Anderson Cancer Center, Houston (G.N.H.).
Address reprint requests to Dr. Baselga at the Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, 55 Fruit St., Lawrence House 108, Boston, MA 02114, or at jbaselga@partners.org.

 

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