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Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer

Fabrice André ... 肿瘤 • 2019.05.16
• 氟维司群联合阿那曲唑治疗转移性乳腺癌的患者总生存期 • 依维莫司治疗绝经后激素受体阳性的晚期乳腺癌






在一项随机、3期试验中,我们在既往接受过内分泌治疗的HR阳性、HER2阴性晚期乳腺癌患者中比较了alpelisib(剂量为每日300 mg)+氟维司群(在第1周期的第1日和第15日以及随后各28日周期的第1日给药,剂量500 mg)治疗与安慰剂+氟维司群治疗。根据肿瘤组织PIK3CA突变状态,患者被纳入两个队列。主要终点为在PIK3CA突变癌症队列中,研究者判定的无进展生存期;本试验还在无PIK3CA突变癌症队列中评估了无进展生存期。次要终点包括总缓解率和安全性。



共计572例患者被随机分组,包括经证实有肿瘤组织PIK3CA突变的341例患者。在PIK3CA突变癌症患者队列中,在alpelisib-氟维司群组和安慰剂-氟维司群组中,中位随访20个月时的无进展生存期分别为11.0个月(95%置信区间[CI],7.5~14.5)和5.7个月(95% CI,3.7~7.4)(进展或死亡的风险比,0.65;95% CI,0.50~0.85;P<0.001);在无PIK3CA突变癌症队列中,风险比为0.85(95% CI,0.58~1.25;风险比的后验概率<1.00,79.4%)。在无PIK3CA突变癌症队列中,alpelisib-氟维司群治疗的总缓解率高于安慰剂-氟维司群治疗(26.6% vs. 12.8%);在这一队列的有可测量病变的患者中,总缓解率分别为35.7%和16.2%。在全部人群中,最常见的3级或4级不良事件为高血糖(alpelisib-氟维司群组36.6% vs.安慰剂-氟维司群组0.7%)和皮疹(9.9% vs. 0.3%)。在alpelisib-氟维司群组和安慰剂-氟维司群组中,3级腹泻发生率分别为6.7%和0.3%;无关于4级腹泻的报道。因不良事件停止alpelisib和安慰剂治疗的患者百分比分别为25.0%和4.2%。





Fabrice André, M.D., Eva Ciruelos, M.D., Gabor Rubovszky, M.D., Mario Campone, M.D., Sibylle Loibl, M.D., Hope S. Rugo, M.D., Hiroji Iwata, M.D., Pierfranco Conte, M.D., Ingrid A. Mayer, M.D., Bella Kaufman, M.D., Toshinari Yamashita, M.D., Yen-Shen Lu, M.D., Kenichi Inoue, M.D., Masato Takahashi, M.D., Zsuzsanna Pápai, M.D., Anne-Sophie Longin, M.Sc., David Mills, M.Sc., Celine Wilke, M.D., Samit Hirawat, M.D., and Dejan Juric, M.D. for the SOLAR-1 Study Group*
From Institut Gustave Roussy, INSERM Unité 981, Université Paris-Sud, Villejuif (F.A.), Institut de Cancérologie de l’Ouest, St. Herblain (M.C.), and Novartis Pharma, Paris (A.-S.L.) — all in France; Hospital Universitario 12 de Octubre, Madrid (E.C.); National Institute of Oncology (G.R.) and Duna Medical Center (Z.P.), Budapest, Hungary; German Breast Group, Neu-Isenburg, and Center for Hematology and Oncology Bethanien, Frankfurt — both in Germany (S.L.); UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.); Aichi Cancer Center, Nagoya (H.I.), Kanagawa Cancer Center, Yokohama (T.Y.), Saitama Cancer Center, Saitama (K.I.), and National Hospital Organization Hokkaido Cancer Center, Sapporo (M.T.) — all in Japan; Istituto Oncologico Veneto and the Departments of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy (P.C.); Vanderbilt University, Nashville (I.A.M.); Chaim Sheba Medical Center, Tel Hashomer, Israel (B.K.); National Taiwan University Hospital, Taipei (Y.-S.L.); Novartis Pharma, Basel, Switzerland (D.M., C.W.); Novartis Pharmaceuticals, East Hanover, NJ (S.H.); and Massachusetts General Hospital Cancer Center, Boston (D.J.). Address reprint requests to Dr. André at Institut Gustave Roussy, 114 Rue Edouard Vaillant, Villejuif, 94805, France, or at fabrice.andre@gustaveroussy.fr; or to Dr. Juric at Massachusetts General Hospital Cancer Center, 55 Fruit St., Boston, MA 02114, or at juric.dejan@mgh.harvard.edu. *A complete list of the investigators in the SOLAR-1 Study Group is provided in the Supplementary Appendix, available at NEJM.org.



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