Yanev Ivan, Aprikian Armen G, Raizenne Brendan L, Dragomir Alice
Centre for Outcomes Research and Evaluation, Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Experimental Surgery, McGill University, Montreal, QC H3A 0G4, Canada.
Cancers (Basel). 2024 Dec 26;17(1):40. doi: 10.3390/cancers17010040.
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.
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.
背景/目的：通过III期临床试验，聚（ADP-核糖）聚合酶（PARP）抑制剂已证明，对于在第二代雄激素受体通路抑制剂（ARPI）治疗期间病情进展、存在BRCA1/2基因改变的转移性去势抵抗性前列腺癌（mCRPC）患者，其治疗效果有所改善。在改善治疗效果的同时，PARP抑制剂也使前列腺癌（PCa）的经济负担不断加重。本项目的目的是从加拿大医疗保健系统的角度，评估PARP抑制剂（奥拉帕利、鲁卡帕利或他拉唑帕利）与标准治疗（多西他赛或雄激素受体通路抑制剂（ARPI））相比，对于既往病情进展的BRCA1/2突变mCRPC患者的成本效益。
构建分区生存模型，以代表病情进展直至死亡后的mCRPC疾病。BRCA1/2突变患者的生存数据取自PROfound、TRITON3和TALAPRO-1临床试验，而加拿大特定成本以2023年的美元表示。病情进展后，患者接受化疗。考虑的时间范围为5年，结果按每年1.5%的贴现率进行贴现。
与当前标准治疗相比，PARP抑制剂可使质量调整生命年（QALY）增加0.19，额外成本为101,679加元，导致增量成本效用比（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（WTP）阈值。
虽然PARP抑制剂能为既往病情进展、存在有害BRCA1/2基因突变的mCRPC患者带来生存益处，但它们不具有成本效益，需要大幅降价才能达到当地的WTP阈值。
