{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:45:41Z","timestamp":1789062341624,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The current guidelines for treating metastatic castration\u2010sensitive prostate cancer (mCSPC) recommend treatment intensification of androgen deprivation therapy (ADT) with the addition of an androgen receptor pathway inhibitor (ARPI), with or without docetaxel. However, the adoption of these treatment options has been slow, leading to therapeutic inertia. This real\u2010world study was conducted to investigate the occurrence of adverse events (AEs) among treated patients diagnosed with mCSPC in the United States.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective claim review estimated the occurrence of AEs among patients with mCSPC from January 2014 to June 2021 in the PharMetrics\u00ae Plus data set. The study focused on 10 common AEs (fatigue\/asthenia, gastrointestinal [GI] AEs, skin\/nail\/hair AEs, immunodeficiency\/thrombocytopenia, hot flash, sexual function AEs, anemia, hypertension, pain, and edema) known to occur in \u226510% of patients and \u22652% more prevalent than those treated with ADT alone as selected from the US Food and Drug Administration prescribing information and published results from clinical trials. Proportions of patients experiencing these AEs at Day 90, 180, and then every 180 days until month 30 during the follow\u2010up period were estimated using cumulative hazard plots. Results were adjusted using inverse probability of treatment weighting (IPTW) across four treatment groups: ADT alone, ADT\u2009+\u2009nonsteroidal anti\u2010androgen (NSAA) (bicalutamide, nilutamide, or flutamide), ADT\u2009+\u2009docetaxel, and ADT\u2009+\u2009ARPIs (abiraterone, apalutamide, or enzalutamide). ADT\u2010alone cohort was the reference group for all comparisons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 4145 patients were included (ADT alone: 2318, ADT\u2009+\u2009NSAA: 632, ADT\u2009+\u2009docetaxel: 471, ADT\u2009+\u2009ARPIs: 724). At baseline, median (interquartile range [IQR]) age was 64.3 (60.1\u201373.1) years; most common sites of metastasis were bone only (<jats:italic>n<\/jats:italic>\u2009=\u20091886, 45.5%) and node only (<jats:italic>n<\/jats:italic>\u2009=\u20091237, 29.8%); most used medications were pain medications (<jats:italic>n<\/jats:italic>\u2009=\u20092182, 52.6%) and corticosteroids (<jats:italic>n<\/jats:italic>\u2009=\u20091213, 29.3%). Median (IQR) duration of follow\u2010up 10.2 (6.1\u201316.6) months in ADT alone, 6.7 (4.1\u201311.5) months in ADT\u2009+\u2009NSAA, 5.1 (4.3\u20135.9) months in ADT\u2009+\u2009docetaxel, and 11.0 (6.6\u201317.0) months in ADT\u2009+\u2009ARPI cohort. The reported AEs increased over time for all assessed AEs, across all treatment groups. Compared with ADT alone, no statistically significant difference in the proportion of patients with AEs was seen in the ADT\u2009+\u2009ARPI or ADT\u2009+\u2009NSAA cohorts at months 3 and 12; a significantly higher proportion of patients in the ADT\u2009+\u2009docetaxel cohort experienced 6 of the 10 assessed AEs at month 3 (fatigue\/asthenia, GI AEs, skin\/nail\/hair AEs, immunodeficiency\/thrombocytopenia, hot flash, anemia). During the follow\u2010up period, on IPTW analysis, compared with ADT alone, a significantly higher proportion of patients experienced AEs with seven AEs in the ADT + docetaxel group (fatigue\/asthenia, GI AEs, skin\/nail\/hair AEs, immunodeficiency\/thrombocytopenia, hot flash, anemia, edema; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 for all seven), three AEs in the ADT\u2009+\u2009ARPI group (hot flash, <jats:italic>p<\/jats:italic>\u2009=\u20090.05; anemia, <jats:italic>p<\/jats:italic>\u2009=\u20090.01; edema, <jats:italic>p<\/jats:italic>\u2009=\u20090.019), and one AE in the ADT\u2009+\u2009NSAA group (anemia, <jats:italic>p<\/jats:italic>\u2009=\u20090.029). The proportion of patients with sexual function AE did not significantly differ between the treatment groups and ADT alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Results of this large, real\u2010world study demonstrated that all treatment groups experienced an increase in the rates of AEs over time, including ADT alone. Most AE rates with ADT\u2009+\u2009ARPIs were comparable with ADT\u2009+\u2009NSAA and not significantly different from ADT alone. ADT\u2009+\u2009docetaxel cohort was associated with significantly higher rates for all AEs over time except hypertension, sexual dysfunction, and pain. This study provides real\u2010world evidence on AEs, beyond controlled clinical trials, and may assist healthcare providers to make better\u2010informed decisions about disease management among patients with mCSPC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24777","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T10:15:25Z","timestamp":1724148925000},"page":"1387-1397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Real\u2010world prevalence of adverse events with first\u2010line systemic therapies among patients with metastatic castration\u2010sensitive prostate cancer"],"prefix":"10.1002","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3518-0411","authenticated-orcid":false,"given":"Umang","family":"Swami","sequence":"first","affiliation":[{"name":"Huntsman Cancer Institute University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xie","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc. Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Young","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc. Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan","family":"Ramaswamy","sequence":"additional","affiliation":[{"name":"Pfizer Inc. New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"El\u2010Chaar","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc. Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"Analysis Group Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Yang","sequence":"additional","affiliation":[{"name":"Analysis Group Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Analysis Group Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Mucha","sequence":"additional","affiliation":[{"name":"Astellas Pharma Inc. Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_9_3_1","unstructured":"National Cancer Institute; Surveillance Epidemiology and End Results Program: SEER Incidence; Prostate Recent Trends in SEER Age\u2010Adjusted Incidence Rates 2004\u20102020. 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NCCN makes no warranties of any kind whatsoever regarding their content use or application and disclaims any responsibility for their application or use in any way."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000002121"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13194951"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2022.06.017"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2023-0814"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000003370"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.5065"},{"key":"e_1_2_9_16_1","unstructured":"Center for Disease Control and Prevention; National Center for Health Statistics; International Classification of Diseases Tenth Revision Clinical Modification (ICD\u201010\u2010CM). 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