{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:41:43Z","timestamp":1790671303452,"version":"4.1.0"},"reference-count":29,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>The impact of statins on overall survival (OS) in patients with prostate cancer treated using intensified therapy with apalutamide is not fully understood.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine whether statin exposure was associated with OS and grade 3 or greater cardiac adverse events (AEs) in patients treated with apalutamide.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This cohort study used individual patient data from 2 multicenter phase 3 randomized clinical trials, SPARTAN (October 14, 2013, to December 15, 2016) and TITAN (December 15, 2015, to July 25, 2017). The final analysis was done on May 21, 2025. TITAN and SPARTAN randomized patients to receive androgen deprivation therapy with or without apalutamide in metastatic hormone-sensitive prostate cancer (TITAN) and nonmetastatic castration-resistant prostate cancer (SPARTAN).<\/jats:p><\/jats:sec>Exposure<\/jats:title>Statin exposure during the assigned treatment; statin exposure could have started before and ended either during or after the assigned treatment.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Inverse probability of treatment\u2013weighted (IPTW) multivariable Cox proportional hazard regression model and covariate-adjusted OS were estimated for patients with and without statin exposure in each trial. Fine and Gray regression models were applied to determine the association of statin exposure with risk of grade 3 or greater cardiac AEs, considering deaths as competing events.<\/jats:p><\/jats:sec>Results<\/jats:title>Among 2187 patients included in this analysis, 1288 received apalutamide (517 in TITAN; 770 in SPARTAN) and 900 received placebo. The median (IQR) age was 65 (60-70) years in TITAN and 70 (65-80) years in SPARTAN. Patients with statin exposure were older with higher body mass index, while the proportion of patients with ECOG performance status score 1 was relatively lower. Statin exposure was associated with superior OS in patients treated with apalutamide (TITAN: hazard ratio [HR], 0.53; 95% CI, 0.32-0.87; SPARTAN: HR, 0.54; 95% CI, 0.39-0.74), but not in patients who received the placebo (TITAN: HR, 0.65; 95% CI, 0.38-1.13; SPARTAN: HR, 1.16; 95% CI, 0.76-1.77). Covariate-adjusted 3-year OS among patients with vs without statins were 81% vs 67% (difference, 14% [95% CI, 5%-22%]) and 86% vs 78% (difference, 8% [95% CI, 3%-13%]) in the apalutamide-treated patients from TITAN and SPARTAN trials, respectively. Patients receiving statins had a higher risk of grade 3 or higher cardiac AEs in both apalutamide (subdistribution HR, 2.62 [95% CI, 1.35-5.08]) and placebo (subdistribution HR, 2.36 [95% CI, 0.96-5.84]) groups.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this cohort study, statin exposure was associated with longer OS in patients treated with apalutamide. Statin-exposed patients had a higher risk of grade 3 or greater cardiac AEs, which may reflect their preexisting cardiovascular comorbidity.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.27988","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T15:00:28Z","timestamp":1755702028000},"page":"e2527988","source":"Crossref","is-referenced-by-count":8,"title":["Statin Use in Patients With Advanced Prostate Cancer in the TITAN and SPARTAN Trials"],"prefix":"10.1001","volume":"8","author":[{"given":"Soumyajit","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep Irem","family":"Ozay","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avirup","family":"Guha","sequence":"additional","affiliation":[{"name":"Cardio-Oncology Program, Georgia Cancer Center, Augusta University, Augusta, Georgia"},{"name":"Division of Cardiology, Department of Medicine, Medical College of Georgia, Augusta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim N.","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, BC Cancer \u2013 Vancouver, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical Physics, and Radiology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Malone","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical Physics, and Radiology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J. 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