奥拉帕利治疗携种系 BRCA 突变的转移性乳腺癌患者。
Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.
机构信息
From the Memorial Sloan Kettering Cancer Center, New York (M.R.); Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); Medical University of Gdańsk, Gdańsk, Poland (E.S.); National Cancer Center-Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (B.X.), and the First Hospital of Jilin University, Changchun (W.L.) - both in China; Basser Center, University of Pennsylvania, Philadelphia (S.M.D.); National Hospital Organization, Osaka National Hospital, Osaka, Japan (N.M.); Institut Gustave Roussy, Villejuif, France (S.D.); Beth Israel Deaconess Medical Center, Dana-Farber Harvard Cancer Center, Boston (N.T.); Christie Hospital NHS Foundation Trust and Faculty of Biology, Medicine and Health, University of Manchester, Manchester (A.A.), and AstraZeneca, Macclesfield (S.R.) - both in the United Kingdom; AstraZeneca, Gaithersburg, MD (W.W., C.G.); and University of Padua and Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy (P.C.).
出版信息
N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4.
BACKGROUND
Olaparib is an oral poly(adenosine diphosphate-ribose) polymerase inhibitor that has promising antitumor activity in patients with metastatic breast cancer and a germline BRCA mutation.
METHODS
We conducted a randomized, open-label, phase 3 trial in which olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease. Patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or standard therapy with single-agent chemotherapy of the physician's choice (capecitabine, eribulin, or vinorelbine in 21-day cycles). The primary end point was progression-free survival, which was assessed by blinded independent central review and was analyzed on an intention-to-treat basis.
RESULTS
Of the 302 patients who underwent randomization, 205 were assigned to receive olaparib and 97 were assigned to receive standard therapy. Median progression-free survival was significantly longer in the olaparib group than in the standard-therapy group (7.0 months vs. 4.2 months; hazard ratio for disease progression or death, 0.58; 95% confidence interval, 0.43 to 0.80; P<0.001). The response rate was 59.9% in the olaparib group and 28.8% in the standard-therapy group. The rate of grade 3 or higher adverse events was 36.6% in the olaparib group and 50.5% in the standard-therapy group, and the rate of treatment discontinuation due to toxic effects was 4.9% and 7.7%, respectively.
CONCLUSIONS
Among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with olaparib monotherapy than with standard therapy. (Funded by AstraZeneca; OlympiAD ClinicalTrials.gov number, NCT02000622 .).
背景
奥拉帕利是一种口服聚（二腺苷二磷酸核糖）聚合酶抑制剂，在转移性乳腺癌和种系 BRCA 突变的患者中具有有前景的抗肿瘤活性。
方法
我们进行了一项随机、开放标签、3 期试验，比较了奥拉帕利单药治疗与标准治疗在种系 BRCA 突变和人表皮生长因子受体 2（HER2）阴性转移性乳腺癌患者中的疗效，这些患者接受转移性疾病的最多两线化疗后。患者按 2:1 的比例随机分配，接受奥拉帕利片（每日两次，每次 300mg）或标准治疗，即医生选择的单药化疗（卡培他滨、艾日布林或长春瑞滨，每 21 天为一个周期）。主要终点是无进展生存期，通过盲法独立中心审查评估，并按意向治疗进行分析。
结果
在 302 名接受随机分组的患者中，205 名患者被分配接受奥拉帕利治疗，97 名患者被分配接受标准治疗。奥拉帕利组的无进展生存期明显长于标准治疗组（7.0 个月 vs. 4.2 个月；疾病进展或死亡的风险比，0.58；95%置信区间，0.43 至 0.80；P<0.001）。奥拉帕利组的缓解率为 59.9%，标准治疗组为 28.8%。奥拉帕利组的 3 级或以上不良事件发生率为 36.6%，标准治疗组为 50.5%，因毒性反应而停止治疗的发生率分别为 4.9%和 7.7%。
结论
在 HER2 阴性转移性乳腺癌和种系 BRCA 突变的患者中，奥拉帕利单药治疗比标准治疗显著获益；与标准治疗相比，奥拉帕利单药治疗可使中位无进展生存期延长 2.8 个月，疾病进展或死亡风险降低 42%。（由阿斯利康公司资助；OlympiAD 临床试验.gov 编号，NCT02000622）。
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