Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.
JAMA Netw Open. 2020 Dec 1;3(12):e2028620. doi: 10.1001/jamanetworkopen.2020.28620.
There are large randomized clinical trials-SOLO-1 (Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy [December 2018]), PRIMA (A Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy [September 2019]), and PAOLA-1 (Platine, Avastin and Olaparib in 1st Line [December 2019])-reporting positive efficacy results for maintenance regimens for women with primary, advanced epithelial ovarian cancer. The findings resulted in approval by the US Food and Drug Administration of the treatments studied as of May 2020. However, there are pressing economic considerations given the many eligible patients and substantial associated costs.
To evaluate the cost-effectiveness of maintenance strategies for patients with (1) a BRCA variant, (2) homologous recombination deficiency without a BRCA variant, or (3) homologous recombination proficiency.
DESIGN, SETTING, AND PARTICIPANTS: In this economic evaluation of the US health care sector using simulated patients with primary epithelial ovarian cancer, 3 decision trees were developed, one for each molecular signature. The maintenance strategies evaluated were olaparib (SOLO-1), olaparib-bevacizumab (PAOLA-1), bevacizumab (PAOLA-1), and niraparib (PRIMA). Base case 1 assessed olaparib, olaparib-bevacizumab, bevacizumab, and niraparib vs observation of a patient with a BRCA variant. Base case 2 assessed olaparib-bevacizumab, bevacizumab, and niraparib vs observation in a patient with homologous recombination deficiency without a BRCA variant. Base case 3 assessed olaparib-bevacizumab, bevacizumab, and niraparib vs observation in a patient with homologous recombination proficiency. The time horizon was 24 months. Costs were estimated from Medicare claims, wholesale acquisition prices, and published sources. Probabilistic sensitivity analyses with microsimulation were then conducted to account for uncertainty and assess model stability. One-way sensitivity analyses were also performed. The study was performed from January through June 2020.
Incremental cost-effectiveness ratios (ICERs) in US dollars per progression-free life-year saved (PF-LYS).
Assuming a willingness-to-pay threshold of $100 000/PF-LYS, none of the drugs could be considered cost-effective compared with observation. In the case of a patient with a BRCA variant, olaparib was the most cost-effective (ICER, $186 777/PF-LYS). The third-party payer price per month of olaparib would need to be reduced from approximately $17 000 to $9000 to be considered cost-effective. Olaparib-bevacizumab was the most cost-effective in the case of a patient with homologous recombination deficiency without a BRCA variant (ICER, $629 347/PF-LYS), and bevacizumab was the most cost-effective in the case of patient with homologous recombination proficiency (ICER, $557 865/PF-LYS). Even at a price of $0 per month, niraparib could not be considered cost-effective as a maintenance strategy for patients with homologous recombination proficiency.
The findings of this study suggest that, at current costs, maintenance therapy for primary ovarian cancer is not cost-effective, regardless of molecular signature. For certain therapies, lowering the drug price alone may not make them cost-effective.
有几项大型随机临床试验——SOLO-1(奥拉帕利维持治疗在一线铂类化疗后携带 BRCA 突变的卵巢癌患者中的应用[2018 年 12 月])、PRIMA(尼拉帕利维持治疗在一线铂类化疗后反应的晚期卵巢癌患者中的应用[2019 年 9 月])和 PAOLA-1(Platine、Avastin 和 Olaparib 在一线治疗中的应用[2019 年 12 月])——报告了针对原发性晚期上皮性卵巢癌患者的维持治疗方案的阳性疗效结果。这些发现导致美国食品和药物管理局在 2020 年 5 月批准了所研究的治疗方法。然而,鉴于有许多合格的患者和大量相关费用,存在紧迫的经济考虑因素。
评估维持治疗策略在以下患者中的成本效益:(1)存在 BRCA 变异,(2)存在同源重组缺陷但不存在 BRCA 变异,或(3)存在同源重组功能。
设计、设置和参与者:在这项针对美国卫生保健部门的经济学评价中,使用原发性上皮性卵巢癌的模拟患者,开发了 3 个决策树,每个分子特征一个。评估的维持治疗策略包括奥拉帕利(SOLO-1)、奥拉帕利联合贝伐珠单抗(PAOLA-1)、贝伐珠单抗(PAOLA-1)和尼拉帕利(PRIMA)。基础病例 1 评估了奥拉帕利、奥拉帕利联合贝伐珠单抗、贝伐珠单抗和尼拉帕利与携带 BRCA 变异的患者观察治疗相比的情况。基础病例 2 评估了奥拉帕利联合贝伐珠单抗、贝伐珠单抗和尼拉帕利与不存在 BRCA 变异的同源重组缺陷患者观察治疗相比的情况。基础病例 3 评估了奥拉帕利联合贝伐珠单抗、贝伐珠单抗和尼拉帕利与同源重组功能正常的患者观察治疗相比的情况。时间范围为 24 个月。成本是根据医疗保险索赔、批发采购价格和已发表的资料进行估算的。然后使用微模拟进行概率敏感性分析,以考虑不确定性并评估模型稳定性。还进行了单因素敏感性分析。研究于 2020 年 1 月至 6 月进行。
增量成本效果比(ICERs),以每无进展生存生命年(PF-LYS)节省的美元表示。
假设支付意愿阈值为每 PF-LYS 100000 美元,与观察治疗相比,这些药物均不能被认为是具有成本效益的。对于存在 BRCA 变异的患者,奥拉帕利是最具成本效益的(ICER,每 PF-LYS 186777 美元)。每月奥拉帕利的第三方支付价格需要从大约 17000 美元降低到 9000 美元才能被认为是具有成本效益的。对于不存在 BRCA 变异的同源重组缺陷患者,奥拉帕利联合贝伐珠单抗是最具成本效益的(ICER,每 PF-LYS 629347 美元),而对于同源重组功能正常的患者,贝伐珠单抗是最具成本效益的(ICER,每 PF-LYS 557865 美元)。即使价格为每月 0 美元,尼拉帕利也不能被认为是具有成本效益的同源重组功能正常患者的维持治疗策略。
这项研究的结果表明,在目前的成本下,原发性卵巢癌的维持治疗不具有成本效益,无论分子特征如何。对于某些疗法,仅降低药物价格可能不会使其具有成本效益。