Real-world cost effectiveness of androgen receptor pathway inhibitors for metastatic hormone sensitive prostate cancer: An economic evaluation utilizing data from the International Registry for Men with Advanced Prostate Cancer (IRONMAN).

11164 Background: Several therapies are approved for metastatic hormone sensitive prostate cancer (mHSPC), with differing efficacy and costs. While many cost-effectiveness analyses (CEAs) rely on randomized trial data, such analyses lack generalizability to real-world practice. We evaluated the real-world cost effectiveness (CE) of adding androgen receptor pathway inhibitors (ARPIs) to androgen deprivation therapy (ADT) for first-line (1L) mHSPC using the IRONMAN registry (NCT03151629). Methods: We conducted a US public payer perspective CEA using individual patient-level IRONMAN data. Eligible patients (pts) received 1L ADT alone, ADT + enzalutamide (ENZ), or ADT + apalutamide (APA) with ≥1 follow-up visit. A 3-state Markov model with 1-month cycles and a 10-year horizon was used. Progression-free survival (PFS) was proxied by time-to-next-treatment (TTNT); overall survival (OS) was time from 1L initiation to death or last follow-up. Costs and outcomes were discounted at 3% per year. Outcomes were measured in life-years gained (LYG) and incremental cost-effectiveness ratios (ICER) were reported. Uncertainty was assessed via one-way sensitivity analysis and probabilistic sensitivity analysis. A scenario analysis evaluated hypothetical ENZ price reductions aligned with planned Inflation Reduction Act negotiations. Results: 1187 pts with mHSPC met inclusion (ADT: n=405, ENZ: n=412, APA: n=370; Table 1). In the base case, both ARPI strategies improved OS versus ADT alone, though only APA provided a statistically significant reduction in risk (ENZ: HR 0.78, 95% CI 0.58-1.03, p=0.08; APA: HR 0.50, 95% CI 0.36-0.70, p<0.001). Using TTNT as a proxy for PFS, ADT alone had a reduced risk compared to either ARPI (ENZ: HR 1.97, 95% CI 1.39-2.77, p<0.001; APA: HR 1.51, 95% CI 1.05-2.18, p=0.028); underreporting of subsequent therapies in the ADT alone group may have contributed to this finding. Median follow-up was 26.7 months; median TTNT and OS were not reached. Neither ARPI strategy was CE at conventional US thresholds (ENZ: ICER = $444,947/LYG; APA: ICER = $669,530/LYG), and ENZ would require a 79% price discount to meet CE thresholds. Sensitivity analyses supported the base case results. Conclusions: Adding ENZ or APA to ADT for 1L mHSPC improved OS but was not found to be to be cost-effective at current US prices over a 10-year horizon. Substantial ENZ price reductions would be required to reach commonly used CE thresholds. Baseline characteristics. ADT(N = 405) ENZ(N = 412) APA(N = 370) Median age at study entry (IQR) 71 (64, 78) 71 (65, 76) 71 (65, 76) PSA at study entry (ng/mL) Median (IQR) 9 (1, 53) 4 (1, 21) 3 (0, 13) Range 0, 5430 0, 3560 0, 5530 Missing (%) 137 (34) 62 (15) 56 (15) Duration of follow-up (months)