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卵巢癌的维利帕利联合一线化疗和随后的维利帕利维持治疗
Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer


Robert L. Coleman ... 肿瘤 妇产科和儿科 • 2019.12.19
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摘要


背景

关于高级别浆液性卵巢癌患者初始治疗采用多腺苷二磷酸核糖聚合酶(PARP)抑制剂(如维利帕利[veliparib])联合化疗,以及随后的PARP抑制剂维持治疗的数据有限。

 

方法

在一项国际性3期、安慰剂对照试验中,我们在未经治的Ⅲ期或Ⅳ期高级别浆液性卵巢癌患者中评估了卡铂和紫杉醇一线诱导化疗加用维利帕利,以及随后的维利帕利单药维持治疗的疗效。我们以1∶1∶1的比例将患者随机分组,分别接受化疗+安慰剂治疗及随后的安慰剂维持治疗(对照),化疗+维利帕利治疗及随后的安慰剂维持治疗(维利帕利仅用于联合治疗),或者化疗+维利帕利治疗及随后的维利帕利维持治疗(维利帕利全程治疗)。肿瘤细胞减灭术可在3个周期的试验治疗开始之前或之后实施。联合化疗的持续时间为6个周期,维持治疗的持续时间为30个周期。主要终点是与对照组相比,在维利帕利全程治疗组中,研究者判定的无进展生存期;主要终点是在BRCA突变队列、同源重组缺陷(HRD)(包括BRCA突变队列)队列和意向治疗人群中进行序贯分析。

 

结果

共有1,140例患者被随机分组。在BRCA突变队列中,维利帕利全程治疗组和对照组的中位无进展生存期分别为34.7个月和22.0个月(进展或死亡的风险比,0.44;95%置信区间[CI],0.28~0.68;P<0.001);在HRD队列中,中位无进展生存期分别为31.9个月和20.5个月(风险比,0.57;95 CI,0.43~0.76;P<0.001);在意向治疗人群中,中位无进展生存期分别为23.5个月和17.3个月(风险比,0.68;95% CI,0.56~0.83;P<0.001)。与化疗联用时,维利帕利导致了较高的贫血和血小板减少发生率,以及较高的恶心和疲劳发生率。

 

结论

在全部试验人群中,与仅接受卡铂+紫杉醇诱导治疗相比,卡铂+紫杉醇+维利帕利诱导治疗及随后的维利帕利维持治疗显著延长了患者的无进展生存期。目前不太明确在不采用维利帕利维持治疗的情况下,在诱导治疗期间加用维利帕利的独立价值(由艾伯维公司资助;VELIA/GOG-3005在ClinicalTrials.gov注册号为NCT02470585)。





作者信息

Robert L. Coleman, M.D., Gini F. Fleming, M.D., Mark F. Brady, Ph.D., Elizabeth M. Swisher, M.D., Karina D. Steffensen, M.D., Michael Friedlander, M.B., Ch.B., Ph.D., Aikou Okamoto, M.D., Ph.D., Kathleen N. Moore, M.D., Noa Efrat Ben-Baruch, M.D., Theresa L. Werner, M.D., Noelle G. Cloven, M.D., Ana Oaknin, M.D., Ph.D., Paul A. DiSilvestro, M.D., Mark A. Morgan, M.D., Joo-Hyun Nam, M.D., Charles A. Leath, III, M.D., Shibani Nicum, M.B., Ch.B., Ph.D., Andrea R. Hagemann, M.D., Ramey D. Littell, M.D., David Cella, Ph.D., Sally Baron-Hay, M.D., Jesus Garcia-Donas, M.D., Ph.D., Mika Mizuno, M.D., Ph.D., Katherine Bell-McGuinn, M.D., Ph.D., Danielle M. Sullivan, Ph.D., Bruce A. Bach, M.D., Ph.D., Sudipta Bhattacharya, M.S., Christine K. Ratajczak, Ph.D., Peter J. Ansell, Ph.D., Minh H. Dinh, M.D., Carol Aghajanian, M.D., and Michael A. Bookman, M.D.
From the University of Texas M.D. Anderson Cancer Center, Houston (R.L.C.); University of Chicago Medicine (G.F.F.) and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University (D.C.), Chicago, and AbbVie, North Chicago (D.M.S., B.A.B., S.B., C.K.R., P.J.A., M.H.D.) — all in Illinois; NRG Oncology Statistical and Data Center, Roswell Park Cancer Institute, Buffalo (M.F.B.), and Memorial Sloan Kettering Cancer Center, New York (K.B.-M., C.A.) — both in New York; University of Washington–Seattle Cancer Care Alliance, Seattle (E.M.S.); Lillebaelt University Hospital of Southern Denmark, Vejle, and the University of Southern Denmark, Odense (K.D.S.); Prince of Wales Clinical School, University of New South Wales and Royal Hospital for Women (M.F.), and the Northern Cancer Institute (S.B.-H.), Sydney; Jikei University School of Medicine, Tokyo (A. Okamoto), and Aichi Cancer Center Hospital, Nagoya (M.M.) — both in Japan; Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City (K.N.M.); Kaplan Medical Center, Rehovot, Israel (N.E.B.-B.); Huntsman Cancer Institute, University of Utah, Salt Lake City (T.L.W.); Texas Oncology, U.S. Oncology Research Network, Fort Worth (N.G.C.); Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona (A. Oaknin); Women and Infants Hospital, Providence, RI (P.A.D.); Penn Medicine, Philadelphia (M.A.M.); University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea (J.-H.N.); O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham, Birmingham (C.A.L.); Oxford University Hospitals, Oxford, United Kingdom (S.N.); Washington University School of Medicine, St. Louis (A.R.H.); Kaiser Permanente Northern California, San Francisco (R.D.L., M.A.B.); and H.M. Hospitales–Centro Integral Oncológico H.M. Clara Campal, Madrid (J.G.-D.). Address reprint requests to Dr. Coleman at the University of Texas M.D. Anderson Cancer Center, 1155 Pressler Dr., Houston, TX 77030, or at rcoleman@mdanderson.org. A complete list of investigators in the VELIA/GOG-3005 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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