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.
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.
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).
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.
Cancers. 2024 Dec 26*** epublish ***
Ivan Yanev, Armen G Aprikian, Brendan L Raizenne, Alice Dragomir
Centre for Outcomes Research and Evaluation, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada., Division of Urology, Department of Surgery, McGill University, Montreal, QC H3A 0G4, Canada., Division of Urology, Centre Hospitalier de l'Université de Montréal, 900 St. Denis, Montreal, QC H2X 0A9, Canada., Faculty of Pharmacy, University of Montreal, 2940 Chem. de Polytechnique, Montreal, QC H3T 1J4, Canada.