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N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4.

Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.

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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.).



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.


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.


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.


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 number, NCT02000622 .).

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