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Olaparib for Metastatic Breast Cancer in Patients with a Germline <i>BRCA</i> Mutation

Mark E. RobsonFrom 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 UniversitySeock‐Ah ImSeoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South KoreaElżbieta SenkusFrom 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 UniversityBinghe XuFrom 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 UniversitySusan M. DomchekBasser Center, University of Pennsylvania, PhiladelphiaNorikazu MasudaOsaka National HospitalSuzette DelalogeNational Cancer CenterWěi LiNational Cancer CenterNadine TungBeth Israel Deaconess Medical Center, Dana–Farber Harvard Cancer Center, BostonAnne ArmstrongChristie Hospital NHS Foundation Trust and Faculty of Biology, Medicine and Health, University of Manchester, ManchesterWenting WuAstraZeneca (Japan)Carsten GoesslFrom 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 UniversitySarah RunswickAstraZeneca, MacclesfieldPierFranco ConteNational Cancer Center

2017en

ABI

Annotatsiya

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 .).

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DOI: 10.1056/nejmoa1706450

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