196 Background: Management of metastatic castration-sensitive prostate cancer (mCSPC) continues to evolve. Pivotal trials of androgen deprivation therapy (ADT) intensification with androgen receptor pathway inhibitors established this approach as the preferred first-line treatment for mCSPC, showing meaningful survival benefits; however, unmet clinical needs and financial burden remain. Given high treatment costs and the importance of preferred formulary placement for payer coverage, conducting economic evaluations has become more relevant. We analyzed the cost-effectiveness of darolutamide plus ADT (DAR+ADT) compared with enzalutamide plus ADT (ENZ+ADT) and apalutamide plus ADT (APA+ADT) in progression-free mCSPC. Methods: We developed a partitioned survival model from a U. S. payer perspective over a lifetime horizon with monthly cycles and three health states: mCSPC; metastatic castration-resistant prostate cancer; and death. Patients entered in mCSPC, with transitions determined by progression-free survival and overall survival rates; in the absence of head-to-head trials, clinical outcomes were derived from a network meta-analysis. Parameters included direct costs (2025 USD) and quality-adjusted life years (QALYs) discounted at 3% annually. Outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefits (NMBs) at a 150, 000/QALY willingness-to-pay (WTP) threshold. Red Book informed drug prices (acquisition, administration), while published literature provided costs for grade ≥3 adverse event management and end-of-life care. Results: Lifetime costs ranged from 1, 042, 666 (ENZ+ADT) to 1, 059, 522 (APA+ADT), while QALYs ranged from 3. 990 (APA+ADT) to 4. 182 (DAR+ADT). Compared with ENZ+ADT, DAR+ADT generated 0. 148 additional QALYs at 12, 564 higher costs per patient, resulting in an ICER of 85, 108/QALY. DAR+ADT dominated APA + ADT, providing 0. 192 QALYs with 4, 293 in cost savings per patient. Conclusions: DAR+ADT is a cost-effective first-line therapy for patients with mCSPC from a U. S. payer perspective. Its favorable tolerability and lower adverse event burden reduce downstream costs and improve quality-of-life. Providing seamless open access to DAR expands availability to an evidence-based therapy that can provide favorable patient outcomes at lower overall costs, supporting formulary alignment with clinical value and economic efficiency. This supports providers in selecting optimal regimens without creating affordability barriers, ultimately accelerating time to treatment milestones and reducing long-term healthcare expenditures. Lifetime cost-effectiveness results. Intervention Cost () Δ Cost () QALYs Δ QALYs ICER (/QALYs) NMB (150K WTP) DAR + ADT 1, 055, 229 - 4. 182 - - - ENZ + ADT 1, 042, 666 12, 564 4. 035 0. 148 85, 108 9, 579 APA + ADT 1, 059, 522 (4, 293) 3. 990 0. 192 Dominant 33, 153
Padula et al. (Sun,) studied this question.