Cost effectiveness of eight first-line regimens in metastatic hormone-sensitive prostate cancer (mHSPC) including niraparib + abiraterone acetate/prednisone.

47 Background: An increase in radiographic progression-free survival (PFS) was observed in the AMPLITUDE trial combining androgen deprivation therapy (ADT) with niraparib + abiraterone acetate/prednisone (NAAP) for HRR-deficient metastatic hormone-sensitive prostate cancer (mHSPC) patients (pts). We conducted a cost-effectiveness analysis from a U.S. public-payer perspective comparing NAAP with seven established first-line options for mHSPC of ADT alone and added to ADT; docetaxel (DA); abiraterone (AAP); apalutamide (AAT); enzalutamide (ET); darolutamide + docetaxel (DAD); enzalutamide + docetaxel (EAD). Methods: A partitioned-survival model with monthly cycles over a lifetime horizon (progression-free, post-progression, death) incorporated overall survival (OS) and PFS data derived from survival curves. Drug acquisition costs were from 2025 Federal Supply Schedule (FSS). Administration, subsequent-therapy, and adverse event costs and utilities were obtained from published literature. Costs and outcomes were discounted at 3% annually. Incremental cost-effectiveness ratio (ICER) was estimated at a willingness-to-pay (WTP) threshold of $150,000-$200,000/QALY. Deterministic and probabilistic sensitivity analyses assessed parameter uncertainty. Results: Across eight treatment strategies (N= 9,027 pts) lifetime costs ranged from $41K (ADT) to $730K (DAD) and Quality of Life Years (QALYs) from 3.25 to 4.29. ET, EAD, AAT, DAD, and NAAP regimens were more costly and less effective than alternatives. Among non-dominated options, DA had an ICER of $35,505/QALY vs ADT, and AAP yielded $189,589/QALY. Although DAD achieved the highest lifetime QALYs (4.29), its incremental cost was large (ICER $1.43M/QALY). Conclusions: From a U.S. public-payer perspective, ADT remains the least costly option, but DA is consistently cost-effective, and AAP may be considered cost-effective at higher WTP thresholds. The addition of NAAP offered incremental benefit for patients with HRR-positive mHSPC; however, the ICER using niraparib’s current FSS pricing, derived from the mCRPC setting may limit its overall cost-effectiveness. These findings describe relative economic profiles rather than direct head-to-head comparisons. Cost-effectiveness results (in 2025 US dollars). Regimen Cost ($) Effectiveness (QALYs) ICER (US$/QALY) ADT $41,287 3.25 DA+ADT $60,334 3.79 $35,505 AAP+ADT $67,585 3.83 $189,589 NAAP+ADT $116,712 3.45 Dominated 1 AAT+ADT $361,699 2.43 Dominated 1 ET+ADT $491,283 3.99 Dominated 2 EAD+ADT $562,151 4.16 Dominated 2 DAD+ADT $729,270 4.29 $1,432,592 1 More costly and less effective than another treatment strategy (ie, absolute dominance). 2 More costly and less effective than a linear combination of other treatment strategies (ie, extended dominance).