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.
背景/目的：通过III期临床试验，PARP抑制剂已证明对在接受第二代雄激素受体通路抑制剂（ARPI）治疗后进展的携带BRCA1/2基因突变的转移性去势抵抗性前列腺癌（mCRPC）患者具有改善预后的效果。尽管能改善临床结局，PARP抑制剂也加剧了前列腺癌日益增长的经济负担。本项目旨在从加拿大医疗体系角度，评估PARP抑制剂（奥拉帕利、卢卡帕利或他拉唑帕利）对比标准治疗（多西他赛或雄激素受体通路抑制剂）在既往治疗后进展的携带BRCA1/2突变的mCRPC患者中的成本效益。方法：建立分区生存模型来模拟mCRPC患者从疾病进展至死亡的过程。BRCA1/2突变患者的生存数据来源于PROfound、TRITON3和TALAPRO-1临床试验，加拿大特定成本数据以2023年加元计值。患者疾病进展后接受化疗治疗。研究时间跨度为5年，结果按每年1.5%进行贴现。结果：与当前标准治疗相比，PARP抑制剂可额外获得0.19质量调整生命年（QALY），同时增加101,679加元的成本，增量成本效用比（ICUR）为565,383加元/QALY。结果对PARP抑制剂的采购成本和健康状态效用值最为敏感。PARP抑制剂需要降价高达83%才能达到50,000加元/QALY的支付意愿阈值（WTP）。结论：虽然PARP抑制剂能为既往治疗后进展的携带有害BRCA1/2基因突变的mCRPC患者提供生存获益，但其不具备成本效益，需要大幅降价才能达到当地的支付意愿阈值。
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