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BRCA1或BRCA2突变乳腺癌患者的奥拉帕利辅助治疗
Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer


Andrew N.J. Tutt ... 肿瘤 • 2021.06.24
相关阅读
• OlympiA研究:乳腺癌治疗领域的变局者 • 雌激素受体阳性、HER2阴性乳腺癌的全身性治疗

摘要


背景

多腺苷二磷酸核糖聚合酶抑制剂通过合成致死(synthetic lethality)机制靶向有同源重组修复缺陷的癌症。BRCA1BRCA2生殖细胞系突变相关早期乳腺癌患者需要可减少复发的新疗法。

 

方法

我们开展了一项3期、双盲、随机试验,该试验纳入携带BRCA1BRCA2生殖细胞系致病或可能致病变异体,有高危临床病理因素,并且接受过局部治疗和新辅助或辅助化疗的人表皮生长因子受体2(HER2)阴性早期乳腺癌患者。患者被随机分配(以1∶1的比例)接受为期1年的口服奥拉帕利或安慰剂治疗。主要终点是无浸润性疾病生存率。

 

结果

共计1,836例患者接受了随机分组。本试验在中位随访2.5年时进行了事件驱动的预设期中分析,结果表明奥拉帕利组的3年无浸润性疾病生存率为85.9%,安慰剂组为77.1%(差异,8.8个百分点;95% CI,4.5~13.0;浸润性疾病或死亡的风险比,0.58;99.5% CI,0.41~0.82;P<0.001)。奥拉帕利组的3年无远处疾病生存率为87.5%,安慰剂组为80.4%(差异,7.1个百分点;95% CI,3.0~11.1;远处疾病或死亡的风险比,0.57;99.5% CI,0.39~0.83;P<0.001)。奥拉帕利组的死亡人数少于安慰剂组(两组分别为59和86)(风险比,0.68;99% CI,0.44~1.05;P=0.02);然而,在P<0.01的期中分析界值,组间差异不显著。安全性数据与奥拉帕利的已知副作用一致,无过多严重不良事件或特别关注的不良事件。

 

结论

在携带BRCA1BRCA2生殖细胞系致病或可能致病变异体的高危HER2阴性早期乳腺癌患者中,局部治疗和新辅助或辅助化疗完成后,奥拉帕利辅助治疗组的无浸润性疾病或无远处疾病生存期显著超过安慰剂组。奥拉帕利对患者报告的整体生活质量产生的影响有限(由美国国立癌症研究所和阿斯利康资助,OlympiA在ClinicalTrials.gov注册号为NCT02032823)。





作者信息

Andrew N.J. Tutt, M.B., Ch.B., Ph.D., Judy E. Garber, M.D., M.P.H., Bella Kaufman, M.D., Giuseppe Viale, M.D., Debora Fumagalli, M.D., Ph.D., Priya Rastogi, M.D., Richard D. Gelber, Ph.D., Evandro de Azambuja, M.D., Ph.D., Anitra Fielding, M.B., Ch.B., Judith Balmaña, M.D., Ph.D., Susan M. Domchek, M.D., Karen A. Gelmon, M.D., Simon J. Hollingsworth, Ph.D., Larissa A. Korde, M.D., M.P.H., Barbro Linderholm, M.D., Ph.D., Hanna Bandos, Ph.D., Elżbieta Senkus, M.D., Ph.D., Jennifer M. Suga, M.D., Zhimin Shao, M.D., Andrew W. Pippas, M.D., Zbigniew Nowecki, M.D., Ph.D., Tomasz Huzarski, M.D., Ph.D., Patricia A. Ganz, M.D., Peter C. Lucas, M.D., Ph.D., Nigel Baker, M.Sc., Sibylle Loibl, M.D., Ph.D., Robin McConnell, M.Sc., Martine Piccart, M.D., Ph.D., Rita Schmutzler, M.D., Dr.Med.Habil., Guenther G. Steger, M.D., Joseph P. Costantino, Dr.P.H., Amal Arahmani, Ph.D., Norman Wolmark, M.D., Eleanor McFadden, M.A., Vassiliki Karantza, M.D., Ph.D., Sunil R. Lakhani, M.D., Greg Yothers, Ph.D., Christine Campbell, M.Sc., and Charles E. Geyer, Jr., M.D. for the OlympiA Clinical Trial Steering Committee and Investigators*
From the Breast Cancer Now Toby Robins Research Centre, the Institute of Cancer Research (A.N.J.T.), and the Breast Cancer Now Unit, Guy’s Hospital Cancer Centre, King’s College London (A.N.J.T.), London, AstraZeneca, Cambridge (S.J.H., N.B.), and Frontier Science (Scotland), Kincraig (R.M.C., E.M.F., C.C.) — all in the United Kingdom; Dana–Farber Cancer Institute, Harvard Medical School (J.E.G., R.D.G.), Frontier Science Foundation (R.D.G.), and Harvard T.H. Chan School of Public Health (R.D.G.) — all in Boston; the Breast Oncology Institute, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (B.K.); the University of Milan, European Institute of Oncology IRCCS, Milan (G.V.); Breast International Group (D.F., A.A.) and Institut Jules Bordet, l’Université Libre de Bruxelles (E.A., M.P.), Brussels; NRG Oncology (P.R., H.B., P.C.L., N.W., G.Y., C.E.G.) and the Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania (S.M.D.), Philadelphia, and the UPMC Hillman Cancer Center (P.R., P.C.L., N.W.) and the Department of Biostatistics (H.B., J.P.C., G.Y.), University of Pittsburgh, and the NSABP Foundation (N.W.), Pittsburgh — all in Pennsylvania; AstraZeneca, Gaithersburg (A.F.), and the National Cancer Institute, Rockville (L.A.K.) — both in Maryland; Vall d’Hebron Institute of Oncology and Vall d’Hebron University Hospital (J.B.) — both in Barcelona; BC Cancer, Vancouver, BC, Canada (K.A.G.); Sahlgrenska University Hospital (B.L.) and the Institute of Clinical Sciences, Department of Oncology, Sahlgrenska Academy, Gothenburg University (B.L.) — both in Gothenburg, Sweden; the Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk (E.S.), the Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw (Z.N.), the International Hereditary Cancer Center, Pomeranian Medical University, Szczecin (T.H.), and Read-Gene, Grzepnica (T.H.) — all in Poland; Kaiser Permanente Vallejo Medical Center, Vallejo (J.M.S.), and the UCLA Fielding School of Public Health, David Geffen School of Medicine at UCLA (P.A.G.), and the UCLA Jonsson Comprehensive Cancer Center (P.A.G.), Los Angeles — all in California; Fudan University Shanghai Cancer Center, Shanghai, China, (Z.S.); Georgia NCORP, Northside Hospital Cancer Institute (A.W.P.), and Piedmont Healthcare (A.W.P.) — both in Atlanta; German Breast Group, Neu-Isenburg (S.L.), the Center for Hematology and Oncology Bethanien and Goethe University, Frankfurt (S.L.), and the Center for Familial Breast and Ovarian Cancer and the Center for Integrated Oncology, Faculty of Medicine, University Hospital Cologne, Cologne (R.S.) — all in Germany; the Department of Internal Medicine I and Gaston H. Glock Research Center, Medical University of Vienna, Vienna (G.G.S.); Merck, Kenilworth, NJ (V.K.); the University of Queensland Centre for Clinical Research and Pathology Queensland (S.R.L.) — both in Brisbane, QLD, Australia; and Houston Methodist Cancer Center (C.E.G.) and Weill Cornell Medical College (C.E.G.) — both in Houston. Address reprint requests to Dr. Tutt at the Breast Cancer Now Toby Robins Research Centre, the Institute of Cancer Research, 237 Fulham Rd., London SW3 6JB, United Kingdom, or at andrew.tutt@icr.ac.uk. The members of the OlympiA Steering Committee and the trial investigators are listed in the Supplementary Appendix, available at NEJM.org.

 

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