{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T21:52:20Z","timestamp":1788990740596,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Evidence to guide the treatment for patients with metastatic castration\u2010resistant prostate cancer (mCRPC) and Homologous Recombination Repair (HRR) gene alterations outside of clinical trials remains limited. This was an observational, cohort study, including mCRPC patients with tumor harboring HRR alterations, progressed on a prior androgen receptor pathway inhibitor, and treated with olaparib monotherapy from January 1, 2020, to April 30, 2025. Primary objectives were time on treatment (ToT) and overall survival (OS). Secondary objective was to explore the role of gene and type and location of pathogenic variant (PVs) as potential molecular predictors of olaparib benefit. We included 201 patients in the analysis. No significant differences in OS across distinct HRR gene subgroups were observed (median OS\n                    <jats:italic>BRCA1<\/jats:italic>\n                    \/\n                    <jats:italic>2<\/jats:italic>\n                    vs. non\u2010\n                    <jats:italic>BRCA<\/jats:italic>\n                    HRR: 16.3\u2009months [95% CI, 13.0\u201369.6] vs. 14.2 [95% CI, 12.0\u201322.9;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.681]). Primary refractoriness to olaparib occurred in 36 (18%) patients and was associated with poor survival (1\u2009year\u2010OS rate of primary vs. non\u2010primary refractory: 20% vs. 77%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). The 1\u2009year\u2010ToT rate of\n                    <jats:italic>BRCA1<\/jats:italic>\n                    versus\n                    <jats:italic>BRCA2<\/jats:italic>\n                    was 23% versus 39%, respectively (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.021). Frameshift PVs in the\n                    <jats:italic>BRCA2<\/jats:italic>\n                    gene were a prognostic factor for shorter OS. Differences in OS according to the PV location in the\n                    <jats:italic>BRCA2<\/jats:italic>\n                    functional domains were also significant. Olaparib demonstrated clinical activity in this global, real world, population of mCRPC patients with HRR\u2010altered tumors. Accurately detecting the multitude of variables associated with\n                    <jats:italic>BRCA<\/jats:italic>\n                    genetic variants represents a key area of research potentially affecting the patient's clinical outcomes.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70679","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:39:55Z","timestamp":1787038795000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Global Real\u2010World Outcomes of Olaparib in Metastatic Castration\u2010Resistant Prostate Cancer Patients With Homologous Recombination Repair Alterations"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1199-7286","authenticated-orcid":false,"given":"Lorena","family":"Incorvaia","sequence":"first","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Sciences and Medical\u2010Surgical Biotechnologies, Policlinico Umberto I University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R.","family":"Matrana","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology\/Oncology Ochsner Medical Center  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Maruzzo","sequence":"additional","affiliation":[{"name":"Oncology 3 Unit Istituto Oncologico Veneto \u2010 IOV IRCCS  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray Manneh","family":"Kopp","sequence":"additional","affiliation":[{"name":"Clinical Oncology Sociedad de Oncolog\u00eda y Hematolog\u00eda del Cesar  Valledupar Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3349-5604","authenticated-orcid":false,"given":"Lorenzo","family":"Antonuzzo","sequence":"additional","affiliation":[{"name":"Clinical Oncology Unit Careggi University Hospital  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Bracarda","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera S. Maria  Terni Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2144-6469","authenticated-orcid":false,"given":"Deniz","family":"Tural","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Koc University Medical Faculty  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Procopio","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T.","family":"Bourlon","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orazio","family":"Caffo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Santa Chiara Hospital  Trento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Ignacio","family":"Zapata Laguado","sequence":"additional","affiliation":[{"name":"Clinical Oncology Universidad El Bosque  Bogota Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Di Maio","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Turin, AOU Citt\u00e0 della Salute e della Scienza di Torino  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5423-3158","authenticated-orcid":false,"given":"Brigida Anna","family":"Maiorano","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology IRCCS San Raffaele Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-714X","authenticated-orcid":false,"given":"Vincenza","family":"Conteduca","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Unit of Medical Oncology and Biomolecular Therapy University of Foggia, Policlinico Riuniti  Foggia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Rossetti","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Uro\u2010Gynaecological Oncology Istituto Nazionale Tumori \u2018Fondazione G. Pascale\u2019\u2010IRCCS  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Lipari","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit Ospedale Cannizzaro  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"B\u00fcttner","sequence":"additional","affiliation":[{"name":"Department of Urology University Hospital Bonn (UKB)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimma","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology A.O.U. 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Maria  Terni Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Stellato","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Depetris","sequence":"additional","affiliation":[{"name":"Medical Oncology 1 AOU Citt\u00e0 della Salute e della Scienza, Molinette Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tancredi Didier","family":"Bazan Russo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora Yasbick","family":"Spricido","sequence":"additional","affiliation":[{"name":"Einstein Hospital Israelita  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Bobato Lara","family":"Gismondi","sequence":"additional","affiliation":[{"name":"Einstein Hospital Israelita  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Massari","sequence":"additional","affiliation":[{"name":"Medical Oncology IRCCS Azienda Ospedaliero\u2010Universitaria di Bologna  Bologna Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC) University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pavan","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Urology University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Santoni","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit Macerata Hospital  Macerata Italy"},{"name":"ARON Research Foundation ETS  Macerata Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Taha","sequence":"additional","affiliation":[{"name":"Royal Marsden NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41391\u2010024\u201000901\u20104"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.cell.2015.05.001","article-title":"Integrative Clinical Genomics of Advanced Prostate Cancer","volume":"161","author":"Robinson D.","year":"2015","journal-title":"Cell"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.eururo.2016.08.037","article-title":"DNA Repair in Prostate Cancer: Biology and Clinical Implications","volume":"71","author":"Mateo J.","year":"2017","journal-title":"European Urology"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2023.102650"},{"issue":"14","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1200\/JCO.2012.43.1882","article-title":"Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer","volume":"31","author":"Castro E.","year":"2013","journal-title":"Journal of Clinical Oncology"},{"issue":"6","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.eururo.2019.08.019","article-title":"Interim Results From the IMPACT Study: Evidence for Prostate\u2010Specific Antigen Screening in BRCA2 Mutation Carriers","volume":"76","author":"Page E. 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