{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:41:38Z","timestamp":1792280498147,"version":"4.4.0"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"18","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,6,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Radium-223 is an \u03b1-emitting radiopharmaceutical that improves survival in metastatic castration-resistant prostate cancer (mCRPC). Preclinical data suggest synergy between poly(ADP-ribose) polymerase (PARP) inhibition and radiation. After phase I dose-finding, we conducted a randomized phase II trial to assess efficacy and safety of this combination versus radium-223.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>Men with mCRPC and \u22652 bone metastases (BM) were randomly assigned 1:1 to olaparib (200 mg twice daily) plus radium-223 (55 kBq\/kg intravenous once every 4 weeks \u00d7 6 doses) or radium-223. Crossover was allowed at progression. The primary end point was investigator-assessed radiographic progression-free survival (rPFS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A total of 120 patients were randomly assigned. Most had prior androgen receptor pathway inhibitor exposure (96%), 52% had received docetaxel, 47% had &gt;20 BM, and 90% received bone-protecting agents. The combination significantly improved rPFS (median 8.9\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      4.7 months; hazard ratio [HR], 0.50 [one-sided 90% CI, 0.35 to 0.70]; one-sided\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0042). The benefit was most pronounced in patients without prior docetaxel (13.7\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      5.7 months; HR, 0.24 [90% CI, 0.15 to 0.40]) and those with \u226420 BM (13.4\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      4.2 months; HR, 0.21 [90% CI, 0.13 to 0.33]). The 1-year cumulative incidence of symptomatic skeletal-related events was lower with the combination (12.7%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      22.9%). Median overall survival was similar (20.2\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      21.1 months). Grade \u22653 treatment-related adverse events occurred in 56% versus 33% (combination\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      radium-223), primarily hematologic, including lymphopenia (31%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      9.1%), anemia (22%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      16%), and thrombocytopenia (6.8%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      3.6%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Olaparib plus radium-223 significantly prolonged rPFS compared with radium-223 in men with mCRPC and BM. Despite increased hematologic toxicity, the regimen was manageable and supports further exploration of DNA damage\u2013targeted strategies in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-02835","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T20:00:07Z","timestamp":1778184007000},"page":"1709-1719","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Multicenter, Randomized, Phase II Trial of Olaparib Plus Radium-223 Versus Radium-223 in Men With Castration-Resistant Prostate Cancer With Bone Metastases (COMRADE)"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0581-7963","authenticated-orcid":false,"given":"Rana R.","family":"McKay","sequence":"first","affiliation":[{"name":"University of California San Diego, La Jolla, 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Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0771-9486","authenticated-orcid":false,"given":"Adam","family":"Olson","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7300-7452","authenticated-orcid":false,"given":"Mamta","family":"Parikh","sequence":"additional","affiliation":[{"name":"University of California Davis, Sacramento, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3372-7914","authenticated-orcid":false,"given":"Rahul","family":"Parikh","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center, Kansas City, KS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biren","family":"Saraiya","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, New 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