TOPLINE

ARPIs — abiraterone, apalutamide, and enzalutamide — combined with androgen-deprivation therapy (ADT) were associated with longer progression-free survival vs docetaxel plus ADT in men with metastatic prostate cancer. There were no significant differences among individual ARPIs.

METHODOLOGY

• Researchers used US claims data from the Komodo Healthcare Map database to identify 9141 men with metastatic hormone-sensitive prostate cancer who received ADT plus either docetaxel (24%), abiraterone (43%), apalutamide (12%), or enzalutamide (21%).
• Patients initiated ADT within 4 months of diagnosis and received index treatment (ARPI or docetaxel) within 4 months of ADT initiation between January 2019 and December 2023, with follow-up through June 2025.
• Primary outcomes were progression-free survival and overall survival. Secondary outcomes included time to metastatic castration-resistant prostate cancer (mCRPC) progression and time to new treatment initiation.
• Analysis used Cox proportional hazard models with overlapping propensity score weights to balance baseline characteristics across treatment groups.

TAKEAWAY

• All three ARPI doublets were associated with superior progression-free survival compared with docetaxel: abiraterone (adjusted hazard ratio [aHR], 0.60; 95% CI, 0.55-0.66), apalutamide (aHR, 0.64; 95% CI, 0.56-0.73), and enzalutamide (aHR, 0.57; 95% CI, 0.51-0.64).
• Median progression-free survival was 45.4 months for abiraterone, 42.4 months for apalutamide, 50.5 months for enzalutamide, and 20.9 months for docetaxel.
• No significant differences in overall survival were observed among any of the four doublet regimens, and median overall survival was not reached during the study period.
• All ARPI doublets were associated with reduced risk of mCRPC progression (abiraterone: aHR, 0.52; apalutamide: aHR, 0.59; enzalutamide: aHR, 0.51) and delayed initiation of new treatment (abiraterone: aHR, 0.46; apalutamide: aHR, 0.53; enzalutamide: aHR, 0.47) compared with docetaxel.

IN PRACTICE

"In the absence of head-to-head randomized trials…this study provides comprehensive real-world evidence on the comparative effectiveness of available doublet regimens for [metastatic hormone-sensitive prostate cancer]," the study authors wrote. They added that, "Given similar survival outcomes among ARPI doublets, treatment selection may be guided by cost, toxicity profiles, and patient-specific factors."

SOURCE

The study was led by Ifechukwu B. Nwogu, PhD, MPH, BPharm, of the University of Washington School of Pharmacy in Seattle. It was published online in JCO Oncology Practice.

LIMITATIONS

Claims data lacked clinical variables including prostate-specific antigen values, performance status, and Gleason scores, which may introduce unmeasured confounding. Disease progression was defined using treatment patterns and diagnosis codes, potentially introducing misclassification. The absence of granular data on bone metastasis number and location precluded stratification by disease volume. Darolutamide doublets and triplet therapies were not evaluated.

DISCLOSURES

The study was supported by the University of Washington School of Pharmacy. Several authors reported financial relationships with various pharmaceutical companies, including Neurocrine Biosciences, Metsera, Boehringer Ingelheim, GlaxoSmithKline, and others. Full disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.