Economic evaluation of talazoparib and enzalutamide compared to enzalutamide monotherapy in HRRm metastatic castration-resistant prostate cancer

BACKGROUND: The poly (ADP-ribose) polymerase inhibitor talazoparib, in combination with the androgen receptor pathway inhibitor enzalutamide, has demonstrated improved survival outcomes compared with enzalutamide monotherapy in homologous recombination repair mutations (HRRm)-positive metastatic castration-resistant prostate cancers (mCRPC) in the TALAPRO-2 trial. However, potential cost-effectiveness of the combination regimen remains limited. OBJECTIVES: Our objective was to evaluate lifetime cost-effectiveness of talazoparib plus enzalutamide (TALA + ENZA) versus enzalutamide (ENZA) alone from a U.S. payer perspective. METHODS: A partitioned survival model with progression-free survival and overall survival inputs were derived from the TALAPRO-2. Costs for drugs, adverse events, disease management, and end-of-life care were included. Health outcomes included life-years (LYs) and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) were calculated for TALA + ENZA versus ENZA. Deterministic and probabilistic sensitivity analyses assessed parameter uncertainty, and scenario analyses explored drug price reductions and shorter time horizons. RESULTS: In the base case, TALA + ENZA yielded 4.84 total LYs and 3.25 QALYs, compared with 3.27 LYs and 1.95 QALYs for ENZA alone, resulting in incremental gains of 1.57 LYs and 1.30 QALYs. Total costs were $1,544,791 for TALA + ENZA and $378,932 for ENZA, yielding an ICER of $896,159 per QALY gained. Sensitivity analyses identified utility and drug cost inputs as the most influential parameters. Probabilistic analysis showed a 50% probability of cost-effectiveness at a willingness-to-pay (WTP) threshold of approximately $1.0 million/QALY gained. CONCLUSION: For HRRm-positive mCRPC, TALA + ENZA provided survival and QALY gains compared with ENZA alone but at higher cost, resulting in an ICER exceeding typical U.S. WTP thresholds.