70 Background: Metastatic hormone-sensitive prostate cancer (mHSPC) is an advanced form of prostate cancer with a 5-year survival below 40%. Treatment guidelines recommend androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPIs), docetaxel, or both. However, no head-to-head randomized trials have compared available doublet therapies, and real-world evidence remains limited. This study evaluated the real-world comparative effectiveness of ADT-based doublet regimens. Methods: Using the Komodo Health Claims Database, we identified US men aged ≥18 years with mHSPC who initiated ADT within 4 months of diagnosis. Eligible patients received index treatment with abiraterone, apalutamide, enzalutamide, or docetaxel within 4 months of ADT initiation between January 2019 and December 2023, with follow-up through June 6, 2025. Patients receiving triplet therapy, multiple index treatments, or with other cancer types were excluded. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Progression was defined as time from index treatment date to metastatic castration-resistant prostate cancer (mCRPC), based on treatment initiation and hormone-resistance diagnosis code. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals using overlapping propensity score weights generated from machine learning-based generalized boosted models for confounding adjustment. Results: This study included 9,141 US men with mHSPC (abiraterone + ADT = 3,968; apalutamide + ADT = 1,096; enzalutamide + ADT = 1,902; docetaxel + ADT = 2,175). Each ADT-based ARPI doublet (abiraterone, apalutamide, and enzalutamide) demonstrated superior PFS compared to docetaxel + ADT, primarily due to prolonged time to mCRPC progression. However, no significant differences in PFS were detected among the three ARPI regimens. For OS, no significant differences were observed between any ARPI doublet and docetaxel + ADT, nor within the ARPI regimens. Full survival results are shown in Table 1. Conclusions: Real-world evidence shows superior PFS with each ARPI + ADT regime versus docetaxel + ADT for mHSPC, with comparable OS. Given similar survival outcomes among ARPI doublets, treatment selection may be guided by cost, toxicity profiles, and patient-specific factors. PFS and OS adjusted hazard ratios (aHR). Treatment Comparator PFS: aHR (95% CI) OS: aHR (95% CI) ABI + ADT DOC + ADT 0.55 (0.49 – 0.62) * 0.99 (0.86 – 1.14) APA + ADT DOC + ADT 0.59 (0.54 – 0.65) * 0.91 (0.75 – 1.11) ENZ + ADT DOC + ADT 0.59 (0.51 – 0.67) * 0.88 (0.75 – 1.04) APA + ADT ABI + ADT 0.99 (0.88 – 1.12) 0.92 (0.77 – 1.10) ENZ + ADT ABI + ADT 0.93 (0.84 – 1.03) 0.89 (0.78 – 1.03) APA + ADT ENZ + ADT 1.07 (0.93 – 1.22) 1.03 (0.85 – 1.25) ABI: abiraterone, ADT: androgen deprivation therapy, APA: apalutamide, DOC: docetaxel, ENZ: enzalutamide. *Significant findings.
Nwogu et al. (2026) studied this question.