Cost-effectiveness of talazoparib plus enzalutamide as first-line therapy in metastatic castration-resistant prostate cancer.

Background: The phase III TALAPRO-2 trial established that combining talazoparib (TALA) with enzalutamide significantly extends progression-free survival (PFS) and overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients. Given the substantial cost implications of novel targeted therapies, economic evaluation is essential to determine whether the clinical benefits of this regimen justify its expense in the first-line mCRPC setting. Objectives: To evaluate the cost-effectiveness of talazoparib plus enzalutamide versus enzalutamide monotherapy as first-line treatment for mCRPC, informing clinical decision-making and healthcare resource allocation. Design: A Markov model-based cost-effectiveness analysis. Methods: Based on data from the TALAPRO-2 trial, a dynamic Markov model was constructed to simulate disease progression in mCRPC patients. From the perspectives of U.S. and Chinese payers, total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER) were considered as the primary outputs in the model. One-way sensitivity analysis and probabilistic sensitivity analysis were used to validate the robustness of the model. Price reduction analysis provided an evidence-based basis for drug pricing and health insurance negotiations by quantifying the impact of price adjustments on economics. Results: In the base-case analysis, the ICERs for talazoparib plus enzalutamide were $646,743.72/QALY and $57,635.76/QALY from the U.S. and China perspectives, respectively, which were above the willingness-to-pay thresholds ($150,000 in the U.S. and $40,334 in China). Sensitivity analyses showed that the utility of PFS and drug prices impacted the results most. Price adjustment scenarios showed that China needed a 34.5% price reduction to achieve affordability, whereas the U.S. remained unaffordable even with an 80% price reduction. Conclusion: At current pricing, talazoparib plus enzalutamide as first-line treatment of patients with mCRPC is not cost-effective in either the U.S. or China. The study supports differentiated pricing strategies to balance clinical benefits with the rational allocation of healthcare resources.