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奥拉帕利用于生殖细胞系BRCA突变转移性胰腺癌的维持治疗
Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer


Talia Golan ... 肿瘤 • 2019.07.25
相关阅读
• FOLFIRINOX或吉西他滨作为胰腺癌的辅助治疗 • FOLFIRINOX和吉西他滨用于胰腺癌辅助治疗的比较

摘要


背景

生殖细胞系BRCA1BRCA2突变的患者在转移性胰腺癌患者中占一小部分。多腺苷二磷酸核糖聚合酶(PARP)抑制剂奥拉帕利在该人群中具有抗肿瘤活性。

 

方法

我们开展了一项随机、双盲、安慰剂对照的3期试验,目的是在患转移性胰腺癌且铂类一线化疗期间未发生进展的生殖细胞系BRCA1BRCA2突变患者中评价奥拉帕利维持治疗的疗效。我们以3∶2的比例将患者随机分组,分别接受奥拉帕利片剂(每日2次,每次300 mg)或安慰剂维持治疗。主要终点是通过盲法独立集中审核方式判定的无进展生存期。

 

结果

在接受筛选的3,315例患者中,154例经随机分组并被分配接受试验干预(92例接受奥拉帕利,62例接受安慰剂)。奥拉帕利组的中位无进展生存期显著超过安慰剂组(7.4个月vs. 3.8个月;疾病进展或死亡的风险比,0.53;95%置信区间[CI],0.35~0.82;P=0.004)。在数据成熟度46%的情况下对总生存期进行的期中分析显示,奥拉帕利组和安慰剂组之间无差异(中位数,18.9个月vs. 18.1个月;死亡的风险比,0.91;95% CI,0.56~1.46;P=0.68)。本试验根据欧洲癌症研究和治疗组织的生活质量问卷(European Organization for Research and Treatment of Cancer Quality of Life Questionnaire)评估患者生活质量,生活质量总分(100分量表,较高评分表明生活质量较好)相对于基线的总体变化表明,健康相关生活质量无显著组间差异(组间差异,-2.47分;95% CI,-7.27~2.33)。奥拉帕利组和安慰剂组的3级或更高级别不良事件发生率分别为40%和23%(组间差异,16个百分点;95% CI,-0.02~31);分别有5%和2%的患者因不良事件而停止试验干预。

 

结论

在患转移性胰腺癌的生殖细胞系BRCA突变患者中,奥拉帕利维持治疗的无进展生存期超过安慰剂(由阿斯利康公司等资助;POLO在ClinicalTrials.gov注册号为NCT02184195)。





作者信息

Talia Golan, M.D., Pascal Hammel, M.D., Ph.D., Michele Reni, M.D., Eric Van Cutsem, M.D., Ph.D., Teresa Macarulla, M.D., Ph.D., Michael J. Hall, M.D., Joon-Oh Park, M.D., Ph.D., Daniel Hochhauser, M.D., Ph.D., Dirk Arnold, M.D., Ph.D., Do-Youn Oh, M.D., Ph.D., Anke Reinacher-Schick, M.D., Ph.D., Giampaolo Tortora, M.D., Ph.D., Hana Algül, M.D., Ph.D., M.P.H., Eileen M. O’Reilly, M.D., David McGuinness, M.Sc., Karen Y. Cui, M.D., Ph.D., Katia Schlienger, M.D., Ph.D., Gershon Y. Locker, M.D., and Hedy L. Kindler, M.D.
From the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (T.G.); Hôpital Beaujon (Assistance Publique–Hôpitaux de Paris), Clichy, and University Paris VII, Paris (P.H.); IRCCS Ospedale San Raffaele Scientific Institute, Milan (M.R.), Azienda Ospedaliera Universitaria Integrata Verona, Verona (G.T.), and Fondazione Policlinico Universitario Gemelli IRCCS, Rome (G.T.) — all in Italy; University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona (T.M.); Fox Chase Cancer Center, Philadelphia (M.J.H.); Samsung Medical Center, Sungkyunkwan University School of Medicine (J.-O.P.), and Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine (D.-Y.O.) — both in Seoul, South Korea; University College London Cancer Institute, London (D.H.), and AstraZeneca, Cambridge (D.M.) — both in the United Kingdom; Asklepios Tumorzentrum Hamburg Asklepios Klinik Altona, Hamburg (D.A.), St. Josef-Hospital, Ruhr University Bochum, Bochum (A.R.-S.), and Klinikum rechts der Isar, Department of Internal Medicine II, Technische Universität München, Munich (H.A.) — all in Germany; Memorial Sloan Kettering Cancer Center, New York (E.M.O.); AstraZeneca, Gaithersburg, MD (K.Y.C., G.Y.L.); Merck, Kenilworth, NJ (K.S.); and the University of Chicago, Chicago (H.L.K.) Address reprint requests to Dr. Golan at the Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv 52621, Israel, or at talia.golan@sheba.health.gov.il.

 

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