{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:00:11Z","timestamp":1793829611207,"version":"4.6.1"},"reference-count":43,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:sec id=\"ab-coi220099-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>The effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer (mCSPC) is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi220099-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the comparative effectiveness of contemporary systemic treatment options for patients with mCSPC across clinically relevant subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi220099-6\">\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>For this systematic review and meta-analysis, Ovid MEDLINE and Embase were searched from each database\u2019s inception (MEDLINE, 1946; Embase, 1974) through June 16, 2021. Subsequently, a \u201cliving\u201d auto search was created with weekly updates to identify new evidence as it became available.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi220099-7\">\n                    <jats:title>Study Selection<\/jats:title>\n                    <jats:p>Phase 3 randomized clinical trials (RCTs) assessing first-line treatment options for mCSPC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi220099-8\">\n                    <jats:title>Data Extraction and Synthesis<\/jats:title>\n                    <jats:p>Two independent reviewers extracted data from eligible RCTs. The comparative effectiveness of different treatment options was assessed with a fixed-effect network meta-analysis. Data were analyzed on July 10, 2022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi220099-9\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Outcomes of interest included overall survival (OS), progression-free survival (PFS), grade 3 or higher adverse events, and health-related quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi220099-10\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This report included 10 RCTs with 11\u202f043 patients and 9 unique treatment groups. Median ages of the included population ranged from 63 to 70 years. Current evidence for the overall population suggests that the darolutamide (DARO) triplet (DARO\u2009+\u2009docetaxel [D]\u2009+\u2009androgen deprivation therapy [ADT]; hazard ratio [HR], 0.68; 95% CI, 0.57-0.81), as well as the abiraterone (AAP) triplet (AAP\u2009+\u2009D\u2009+\u2009ADT; HR, 0.75; 95% CI, 0.59-0.95), are associated with improved OS compared with D doublet (D\u2009+\u2009ADT) but not compared with API doublets. Among patients with high-volume disease, AAP\u2009+\u2009D\u2009+\u2009ADT may improve OS compared with D\u2009+\u2009ADT (HR, 0.72; 95% CI, 0.55-0.95) but not compared with AAP\u2009+\u2009ADT, enzalutamide (E)\u2009+\u2009ADT, and apalutamide (APA)\u2009+\u2009ADT. For patients with low-volume disease, AAP\u2009+\u2009D\u2009+\u2009ADT may not improve OS compared with APA\u2009+\u2009ADT, AAP\u2009+\u2009ADT, E\u2009+\u2009ADT, and D\u2009+\u2009ADT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi220099-11\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>The potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.7762","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T11:32:35Z","timestamp":1677756755000},"page":"635","source":"Crossref","is-referenced-by-count":133,"title":["First-line Systemic Treatment Options for Metastatic Castration-Sensitive Prostate Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Irbaz Bin","family":"Riaz","sequence":"first","affiliation":[{"name":"Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, Arizona"},{"name":"Department of Informatics, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, 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