Cost-effectiveness analysis of eight treatments for metastatic hormone-sensitive prostate cancer (mHSPC) stratified by homologous recombination repair (HRR) status.

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e17060 Background: After approval of androgen deprivation therapy (ADT) with niraparib and abiraterone/prednisone (NAAP) for homologous recombination repair (HRR)-deficient mHSPC, we conducted a U.S. public-payer cost-effectiveness analysis (CEA) comparing NAAP with abiraterone/prednisone (AAP). We also assessed CEA for seven established first-line mHSPC options regardless of HRR status: ADT mono, and ADT combined with docetaxel (DA), abiraterone (AAP), apalutamide (AAT), enzalutamide (ET), darolutamide plus docetaxel (DAD), and enzalutamide plus docetaxel (EAD). Methods: A partitioned-survival model with monthly cycles over a lifetime horizon (progression-free, post-progression, death) incorporated overall survival (OS) and radiographic progression free (rPFS) data derived from survival curves. Drug acquisition costs were from 2025 Federal Supply Schedule. Administration, subsequent-therapy, and adverse event costs and utilities were obtained from literature. Incremental cost-effectiveness ratio (ICER) was estimated at a willingness-to-pay (WTP) threshold of $150,000-$200,000/Quality of life Years (QALY). Deterministic and probabilistic sensitivity analyses assessed parameter uncertainty. Results: A CEA model for NAAP Vs. AAP showed that mean lifetime costs were $62,180 for AAP and $768,069 for NAAP. Mean QALYs were higher for NAAP than AAP (3.31vs 3.01). ICER for NAAP was $2.35M/QALY, far exceeding WTP. Across seven treatment strategies (N = 8,333 pts) lifetime costs ranged from $43K (ADT) to $728K (DAD) and Quality of Life Years (QALYs) from 3.38 to 4.42. ET, EAD, and AAT regimens were more costly and less effective than alternatives. Among non-dominated options, DA had an ICER of $30,823/QALY vs ADT, and AAP yielded $314,796/QALY. Although DAD achieved the highest lifetime QALYs (4.42), its incremental cost was large (ICER $1.41M/QALY). Conclusions: From a U.S. public-payer perspective, the addition of NAAP offered incremental benefit for pts with HRR-positive mHSPC; however, the ICER for NAAP was $2.35M/QALY. In mHSPC pts without considering HRR status, DA is consistently cost-effective, and AAP may be considered cost-effective at higher WTP thresholds. Cost-effectiveness results. HRR-deficient mHSPC Cost (2025-USD) Effectiveness (QALY) ICER AAP +ADT $ 62,180 3.01 NAAP +ADT $ 768,069 3.31 $ 2,352,600 non-HRR deficient status ADT mono $ 43,120 3.38 DA $ 59,656 3.92 $ 30,823 AAP +ADT $ 71,878 3.95 $ 314,796 ET $ 359,095 2.57 $ Dominated a EAD $ 493,402 4.12 $ Dominated b AAT $ 558, 518 4.27 $ Dominated b Darolutamide + ADT + Docetaxel (DAD) - results in text. a This treatment strategy is more costly and less effective than another treatment strategy (ie, absolute dominance). b This treatment strategy is more costly and less effective than a linear combination of other treatment strategies (ie, extended dominance).

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