Cost-Effectiveness of PARP Inhibitors for Patients with BRCA1/2-Positive Metastatic Castration-Resistant Prostate Cancer—The Canadian Perspective.

Simple Summary: While considering previously progressed metastatic castration-resistant prostate cancer (mCRPC) patients presenting deleterious BRCA1/2 mutations, poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors provide survival benefits over the current standard of care (SOC). PARP inhibitors are, however, associated with additional costs and their use is constrained by access to genetic testing, potentially placing an economic strain on the healthcare system. This paper aims to assess the cost-effectiveness of PARP inhibitors as a therapeutic class and not only as a single agent, considering approved and soon-to-be approved therapies. This flexible approach considers multiple treatment options comparing the SOC and PARP inhibitors to represent more accurately the clinical management of mCRPC and the potential impact of PARP inhibitors on the treatment landscape. Results from the Canadian healthcare system perspective suggest that PARP inhibitors are not cost-effective. This research impacts policymakers, guiding future reimbursement negotiations and future health economic research in the field. Background/Objectives: Through phase III clinical trials, PARP inhibitors have demonstrated outcome improvements in mCRPC patients with alterations in BRCA1/2 genes who have progressed on a second-generation androgen receptor pathway inhibitor (ARPI). While improving outcomes, PARP inhibitors contribute to the ever-growing economic burden of PCa. The objective of this project is to evaluate the cost-effectiveness of PARP inhibitors (olaparib, rucaparib, or talazoparib) versus the SOC (docetaxel or androgen receptor pathway inhibitors (ARPI)) for previously progressed mCRPC patients with BRCA1/2 mutations from the Canadian healthcare system perspective. Methods: Partitioned survival models were created to represent mCRPC disease after progression until death. Survival inputs for BRCA1/2-mutated patients were extracted from the PROfound, TRITON3, and TALAPRO-1 clinical trials, while Canadian-specific costs are presented in 2023 dollars. Upon progression, patients were treated with chemotherapy. The considered time horizon was 5 years and outcomes were discounted at 1.5% per year. Results: PARP inhibitors provide an additional survival of 0.19 quality-adjusted life years (QALY) when compared to the current standard of care, with additional costs of CAD 101,679 resulting in an incremental cost-utility ratio (ICUR) of CAD 565,383/QALY. The results were most sensitive to PARP inhibitors' acquisition costs and health-state utilities. PARP inhibitors required price reductions of up to 83% to meet the CAD 50,000/QALY willingness-to-pay threshold (WTP). Conclusions: While providing survival benefits to previously progressed mCRPC patients presenting deleterious BRCA1/2 gene mutations, PARP inhibitors are not cost-effective and require major price reductions to reach local WTP thresholds. [ABSTRACT FROM AUTHOR]