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ribociclib对HR阳性晚期乳腺癌一线治疗的研究
Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer


Gabriel N. Hortobagyi ... 肿瘤 • 2016.11.03
相关阅读
• 第40届圣安东尼奥乳腺癌年度研讨会 • CDK4/6新辅助抑制疗法治疗ER阳性乳腺癌

激素受体阳性、HER2阴性的转移性乳腺癌的一线治疗将面临新的选择

 

刘天舒

复旦大学附属中山医院肿瘤内科

 

近日,《新英格兰医学杂志》发表了一项针对激素受体(HR)阳性、人表皮生长因子受体(HER2)阴性的绝经后转移性乳腺癌(MBC)患者的一线治疗的随机对照的三期研究,比较了ribociclib(CDK4/6抑制剂)联合来曲唑对比单用来曲唑的疗效1。该研究在全球29个国家、223个研究中心进行,共纳入了668例患者,中位随访时间15.3个月,达到了预先设置的中期分析结果的目标,联合ribociclib组的18个月的无进展生存期(PFS)比例为63%,对照组为42.2%(风险比0.56),联合组的疗效反应率为52.7%,对照组为37.1%(P<0.001)。安全性数据表明联合ribociclib组的主要毒性是血液学毒性,3/4级白细胞下降的比例是59.3%,粒细胞下降的比例是21%,因毒性反应停药的比例是7.5%。

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摘要


背景

抑制细胞周期蛋白依赖性激酶4和6(CDK4/6)有可能克服或延缓激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性的晚期乳腺癌对内分泌治疗的耐药。

 

方法

在该项随机、安慰剂对照的三期临床试验中,668例HR阳性、HER2阴性的复发或转移性绝经后女性乳腺癌患者参与研究,这些患者此前均未曾接受过针对晚期乳腺癌的全身治疗;在这些患者中,我们评估了选择性CDK4/6抑制剂ribociclib与来曲唑联合一线治疗乳腺癌的疗效和安全性。我们将患者随机分组,分别接受ribociclib(600 mg/d,治疗3周,停药1周)与来曲唑(2.5 mg/d)联合治疗,或安慰剂加来曲唑联合治疗。主要终点为研究者评定的无进展生存期。次要终点包括总生存期、总缓解率和安全性。在243例患者出现疾病进展或死亡后,研究者于2016年1月29日进行了预先计划的中期分析。预先定义的优效性标准要求风险比≤0.56,并且P<1.29×10−5

 

结果

与安慰剂组相比,ribociclib组患者的无进展生存期显著延长(风险比,0.56;95% CI,0.43~0.72;优效性P=3.29×10−6)。中位随访时间为15.3个月。18个月后,ribociclib组患者的无进展生存率为63%(95% CI,54.6~70.3),安慰剂组为42.2%(95% CI,34.8~49.5)。在基线有可测量病灶的患者中,总缓解率分别为52.7%和37.1%(P<0.001)。两组中超过10%患者报告出现的常见3级或4级不良事件包括:中性粒细胞减少(ribociclib组为59.3%对安慰剂组为0.9%)和白细胞减少(21.0%对0.6%);因不良事件而终止治疗的比率分别为7.5%和2.1%。

 

结论

在接受初始全身治疗的HR阳性、HER2阴性的晚期乳腺癌患者中,与安慰剂和来曲唑联合治疗组相比,ribociclib与来曲唑联合治疗组的无进展生存期显著延长,然而骨髓抑制发生率也较高(本项研究由诺华制药公司资助;在ClinicalTrials.gov注册号为NCT01958021)。





作者信息

Gabriel N. Hortobagyi, M.D., Salomon M. Stemmer, M.D., Howard A. Burris, M.D., Yoon-Sim Yap, M.D., Gabe S. Sonke, M.D., Ph.D., Shani Paluch-Shimon, M.D., Mario Campone, M.D., Ph.D., Kimberly L. Blackwell, M.D., Fabrice André, M.D., Ph.D., Eric P. Winer, M.D., Wolfgang Janni, M.D., Ph.D., Sunil Verma, M.D., Pierfranco Conte, M.D., Ph.D., Carlos L. Arteaga, M.D., David A. Cameron, M.D., Katarina Petrakova, M.D., Ph.D., Lowell L. Hart, M.D., Cristian Villanueva, M.D., Arlene Chan, M.D., Erik Jakobsen, M.D., M.P.H., Arnd Nusch, M.D., Olga Burdaeva, M.D., Eva-Maria Grischke, M.D., Emilio Alba, M.D., Ph.D., Erik Wist, M.D., Ph.D., Norbert Marschner, M.D., Anne M. Favret, M.D., Denise Yardley, M.D., Thomas Bachelot, M.D., Ph.D., Ling-Ming Tseng, M.D., Sibel Blau, M.D., Fengjuan Xuan, Ph.D., Farida Souami, M.Sc., Michelle Miller, M.D., Caroline Germa, M.D., Samit Hirawat, M.D., and Joyce O’Shaughnessy, M.D.
Address reprint requests to Dr. Hortobagyi at the Department of Breast Medical Oncology, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, or at ghortoba@mdanderson.org.

 

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