Abstract
BACKGROUND: Talazoparib plus enzalutamide showed significant improvement of progression-free survival in metastatic castration-resistant prostate cancer (mCRPC) patients with alterations in homologous recombination repair (HRR) genes. OBJECTIVES: This study aimed to evaluate the cost-effectiveness of HRR status-guided use of talazoparib plus enzalutamide in patients with mCRPC from the U.S. payer perspective. DESIGN: A partitioned survival model was used to simulate outcomes of a hypothetical cohort of mCRPC patients. METHODS: Three treatment strategies were evaluated: (1) talazoparib plus enzalutamide for HRR-deficient patients and enzalutamide for non-HRR-deficient patients (HRR-guided talazoparib plus enzalutamide), (2) talazoparib plus enzalutamide for patients with or without HRR deficiency (empirical talazoparib plus enzalutamide), and (3) enzalutamide for patients with or without HRR deficiency (empirical enzalutamide). Primary outcomes were direct medical costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost per QALY gained (incremental cost-effectiveness ratio, ICER). Sensitivity analyses were performed to examine the robustness of model results. RESULTS: In base-case analysis, the empirical enzalutamide strategy had the lowest cost and QALYs gained (US$752,383; 2.4764 QALYs), followed by HRR-guided talazoparib plus enzalutamide (US$878,517; 2.6490 QALYs), and empirical talazoparib plus enzalutamide (US$1,201,221; 2.8418 QALYs). The ICER of the HRR-guided talazoparib plus enzalutamide group (vs empirical enzalutamide) was US$730,671 per QALY gained, and the ICER of empirical talazoparib plus enzalutamide (vs HRR-guided talazoparib plus enzalutamide) was US$1,673,457 per QALY gained. Both ICERs of the HRR-guided strategy and empirical combination therapy were higher than the willingness-to-pay threshold (US$100,000 per QALY) and were not accepted as cost-effective. Sensitivity analyses found drug costs of talazoparib and enzalutamide to be the key influential factors on the cost-effectiveness of HRR-guided therapy. CONCLUSION: HRR-guided talazoparib plus enzalutamide does not appear to be cost-effective for mCRPC patients from the U.S. payer perspective.