{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:13:38Z","timestamp":1792088018746,"version":"4.4.0"},"reference-count":28,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2010,5,20]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Selective tumor cell cytotoxicity can be achieved through a synthetic lethal strategy using poly(ADP)-ribose polymerase (PARP) inhibitor therapy in BRCA1\/2 mutation carriers in whom tumor cells have defective homologous recombination (HR) DNA repair. Platinum-based chemotherapy responses correlate with HR DNA repair capacity. Olaparib is a potent, oral PARP inhibitor that is well tolerated, with antitumor activity in BRCA1\/2 mutation carriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Patients with BRCA1\/2-mutated ovarian cancer were treated with olaparib within a dose-escalation and single-stage expansion of a phase I trial. Antitumor activity was subsequently correlated with platinum sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty patients were treated: 48 had germline BRCA1\/2 mutations; one had a BRCA2 germline sequence change of unknown significance, and another had a strong family history of BRCA1\/2-associated cancers who declined mutation testing. Of the 50 patients, 13 had platinum-sensitive disease, 24 had platinum-resistant disease, and 13 had platinum-refractory disease (according to platinum-free interval). Twenty (40%; 95% CI, 26% to 55%) achieved Response Evaluation Criteria in Solid Tumors (RECIST) complete or partial responses and\/or tumor marker (CA125) responses, and three (6.0%) maintained RECIST disease stabilization for more than 4 months, giving an overall clinical benefit rate of 46% (95% CI, 32% to 61%). Median response duration was 28 weeks. There was a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory subgroups (69%, 45%, and 23%, respectively). Post hoc analyses indicated associations between platinum sensitivity and extent of olaparib response (radiologic change, P = .001; CA125 change, P = .002).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Olaparib has antitumor activity in BRCA1\/2 mutation ovarian cancer, which is associated with platinum sensitivity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.2009.26.9589","type":"journal-article","created":{"date-parts":[[2010,4,20]],"date-time":"2010-04-20T22:25:37Z","timestamp":1271802337000},"page":"2512-2519","source":"Crossref","is-referenced-by-count":850,"title":["Poly(ADP)-Ribose Polymerase Inhibition: Frequent Durable Responses in\n                    <i>BRCA<\/i>\n                    Carrier Ovarian Cancer Correlating With Platinum-Free Interval"],"prefix":"10.1200","volume":"28","author":[{"given":"Peter C.","family":"Fong","sequence":"first","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Yap","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Boss","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig P.","family":"Carden","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja","family":"Mergui-Roelvink","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Gourley","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"De Greve","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lubinski","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Shanley","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Messiou","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"A'Hern","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; the Netherlands Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Tutt","sequence":"additional","affiliation":[{"name":"From the Drug Development Unit, Royal Marsden National Health Service Foundation Trust; The Institute of Cancer Research, Sutton, Surrey; Institute of Genetics and Molecular Medicine, University of Edinburgh Cancer Research, Edinburgh; the Breakthrough Breast Cancer Research Unit at King's College London, Guy's Campus; the Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London; AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; 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