Division of Gynecologic Oncology, Duke Cancer Institute, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA.
Int J Gynecol Cancer. 2013 Jun;23(5):846-52. doi: 10.1097/IGC.0b013e31829527bd.
(1) To determine whether use of a PARP inhibitor or (2) BRCA1/2 mutation testing followed by a PARP inhibitor for test positives is potentially cost-effective for maintenance treatment of platinum-sensitive recurrent high-grade serous ovarian cancer.
A modified Markov decision analysis compared 3 strategies: (1) observe; (2) olaparib to progression; (3) BRCA1/2 mutation testing; treat mutation carriers with olaparib to progression. Progression-free survival and rates of adverse events were derived from a phase 2 randomized trial. Key assumptions are as follows: (1) 14% of patients harbor a BRCA1/2 mutation; (2) progression-free survival of individuals treated with olaparib is improved for BCRA1/2 carriers compared with noncarriers (estimated hazard ratio, approximately 0.4). Costs derived from national data were assigned to treatments, adverse events, and BRCA1/2 test. Monte Carlo probabilistic sensitivity analysis was performed.
Global olaparib was the most effective strategy, followed by BRCA1/2 testing and no olaparib. BRCA1/2 testing had an incremental cost-effectiveness ratio (ICER) of $193,442 per progression-free year of life saved (PF-YLS) compared to no olaparib, whereas global olaparib had an ICER of $234,128 per PF-YLS compared to BRCA1/2 testing. At a 52% lower-than-baseline olaparib cost estimate of $3000 per month, BRCA1/2 testing became potentially cost-effective compared with observation, with an ICER of $100,000 per PF-YLS. When strategy (1) was removed from the analysis, BRCA1/2 testing was the preferred strategy.
The use of maintenance olaparib in women with high-grade serous ovarian cancer is not cost-effective regardless of whether BRCA1/2 testing is used to direct treatment. However, BRCA1/2 testing is a preferred strategy compared to global maintenance olaparib alone.
(1)确定使用 PARP 抑制剂或(2)进行 BRCA1/2 突变检测后使用 PARP 抑制剂治疗阳性患者,对于维持治疗铂敏感复发性高级别浆液性卵巢癌是否具有潜在的成本效益。
改良的马尔可夫决策分析比较了 3 种策略:(1)观察;(2)奥拉帕利至进展;(3)BRCA1/2 突变检测;对突变携带者用奥拉帕利治疗至进展。无进展生存期和不良事件发生率来自一项 2 期随机试验。主要假设如下:(1)14%的患者携带 BRCA1/2 突变;(2)与非携带者相比,接受奥拉帕利治疗的个体的无进展生存期得到改善(估计风险比约为 0.4)。从国家数据中得出的成本分配给治疗、不良事件和 BRCA1/2 检测。进行了蒙特卡罗概率敏感性分析。
全球奥拉帕利是最有效的策略,其次是 BRCA1/2 检测和不使用奥拉帕利。与不使用奥拉帕利相比,BRCA1/2 检测的增量成本效益比(ICER)为每延长 1 年无进展生存期(PF-YLS)增加 193442 美元,而全球奥拉帕利的 ICER 为每延长 1 年 PF-YLS 增加 234128 美元,与 BRCA1/2 检测相比。在奥拉帕利每月成本估计降低 52%至 3000 美元的情况下,BRCA1/2 检测与观察相比具有潜在的成本效益,每延长 1 年 PF-YLS 的 ICER 为 10 万美元。当从分析中删除策略 1 时,BRCA1/2 检测成为首选策略。
无论是否使用 BRCA1/2 检测来指导治疗,在高级别浆液性卵巢癌患者中使用维持奥拉帕利治疗都不具有成本效益。然而,与单独使用全球维持奥拉帕利相比,BRCA1/2 检测是一种更优的策略。