{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:30:10Z","timestamp":1790303410015,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30\u2010CA\u2010015704"],"award-info":[{"award-number":["P30\u2010CA\u2010015704"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P50\u2010CA\u2010097186"],"award-info":[{"award-number":["P50\u2010CA\u2010097186"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["T32\u2010CA\u2010009515"],"award-info":[{"award-number":["T32\u2010CA\u2010009515"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["T32\u2010CA\u2010236621"],"award-info":[{"award-number":["T32\u2010CA\u2010236621"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>PARP\u00a0(poly(ADP\u2010ribose) polymerase) inhibitors (PARPi) are now standard of care in metastatic castrate\u2010resistant prostate cancer (mCRPC) patients with select mutations in DNA damage repair (DDR) pathways, but patients with <jats:italic>ATM<\/jats:italic>\u2010 and <jats:italic>BRCA2<\/jats:italic> mutations may respond differently to PARPi. We hypothesized that differences may also exist in response to taxanes, which may inform treatment sequencing decisions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>mCRPC patients (<jats:italic>N<\/jats:italic>\u2009=\u2009158) with deleterious <jats:italic>ATM<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> mutations who received taxanes, PARPi, or both were retrospectively identified from 11 US academic centers. Demographic, treatment, and survival data were collected. Kaplan\u2212Meier analyses were performed and Cox hazard ratios (HR) were calculated for progression\u2010free survival (PFS) as well as overall survival (OS), from time of first taxane or PARPi therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010eight patients with <jats:italic>ATM<\/jats:italic> mutations and 100 with <jats:italic>BRCA2<\/jats:italic> mutations were identified. Fourty\u2010four\u00a0(76%) patients with <jats:italic>ATM<\/jats:italic> mutations received taxane only or taxane before PARPi, while 14 (24%) received PARPi only or PARPi before taxane. Patients with <jats:italic>ATM<\/jats:italic> mutations had longer PFS when taxane was given first versus PARPi given first (HR: 0.74 [95% confidence interval\u00a0[CI]: 0.37\u22121.50]; <jats:italic>p<\/jats:italic>\u2009=\u20090.40). Similarly, OS was longer in patients with <jats:italic>ATM<\/jats:italic> mutations who received taxane first (HR: 0.56 [CI: 0.20\u22121.54]; <jats:italic>p<\/jats:italic>\u2009=\u20090.26). Among patients with <jats:italic>BRCA2<\/jats:italic> mutations, 51 (51%) received taxane first and 49 (49%) received PARPi first. In contrast, patients with <jats:italic>BRCA2<\/jats:italic> mutations had longer PFS when PARPi was given first versus taxane given first (HR: 0.85 [CI: 0.54\u22121.35]; <jats:italic>p<\/jats:italic>\u2009=\u20090.49). Similarly, OS was longer in patients with <jats:italic>BRCA2<\/jats:italic> mutations who received PARPi first (HR: 0.75 [CI: 0.41\u22121.37]; <jats:italic>p<\/jats:italic>\u2009=\u20090.35).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our retrospective data suggest differential response between <jats:italic>ATM<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> mutated prostate cancers in terms of response to PARPi and to taxane chemotherapy. When considering the sequence of PARPi versus taxane chemotherapy for mCRPC with DDR mutations, <jats:italic>ATM<\/jats:italic>, and <jats:italic>BRCA2<\/jats:italic> mutation status may be helpful in guiding choice of initial therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24454","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T09:09:17Z","timestamp":1668589757000},"page":"227-236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Differential responses to taxanes and PARP inhibitors in <i>ATM\u2010<\/i>\u00a0versus <i>BRCA2<\/i>\u2010mutated metastatic castrate\u2010resistant prostate cancer"],"prefix":"10.1002","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2700-2650","authenticated-orcid":false,"given":"Christopher T.","family":"Su","sequence":"first","affiliation":[{"name":"Department of Medicine University of Michigan Ann Arbor Michigan 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Ashkar","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-6503","authenticated-orcid":false,"given":"Alexandra","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro C.","family":"Barata","sequence":"additional","affiliation":[{"name":"Department of Medicine Tulane University New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul R.","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Francisco San Francisco California 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