ArticleTherapeutic advances in urology
Real-world comparative outcomes of darolutamide- versus abiraterone-based triplet therapy for metastatic hormone-sensitive prostate cancer: a retrospective cohort study.
Article in Therapeutic advances in urology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Triplet therapy with androgen deprivation therapy (ADT), docetaxel, and androgen receptor pathway inhibitors (ARPIs), either darolutamide or abiraterone, is one of the standard treatments for metastatic hormone-sensitive prostate cancer (mHSPC); however, no randomized trial has directly compared both ARPIs within this regimen. Given practical and financial constraints, a head-to-head randomized trial directly comparing these ARPIs may be unlikely. Objective: To compare the real-world effectiveness of darolutamide- versus abiraterone-based triplet therapy in patients with mHSPC. Design: Retrospective cohort study using a multinational electronic health record network. Methods: We conducted a retrospective cohort study using the TriNetX research network. Patients with mHSPC treated with darolutamide- or abiraterone-based triplet therapy were identified and balanced using propensity-score matching. The primary outcome was overall survival (OS), and the secondary outcome was time to next treatment (TTNT), defined by treatment switch. Prespecified subgroup analyses focused on age, cardiometabolic comorbidities, and polypharmacy-related medication use. Results: Among 1607 eligible patients, 1252 were included after propensity score matching (626 per group). Darolutamide-based triplet therapy was associated with longer OS compared with abiraterone (hazard ratio (HR) 0.42). A favorable difference in TTNT was also observed (HR 0.66). These associations were consistent across clinically relevant subgroups, including patients aged ⩾65 years and those with ischemic heart disease or diabetes mellitus. In polypharmacy-enriched subgroups, darolutamide-based therapy was consistently associated with more favorable OS and TTNT. Conclusion: In this large real-world analysis, darolutamide-based triplet therapy was associated with longer OS and TTNT compared with abiraterone-based triplet therapy in patients with mHSPC, particularly among older individuals and those with comorbidities. These findings are hypothesis-generating, suggesting that ARPI selection within triplet therapy may have clinically relevant implications, supporting the need for prospective studies.
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