Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States of America; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States of America.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States of America; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States of America.
Gynecol Oncol. 2020 Nov;159(2):483-490. doi: 10.1016/j.ygyno.2020.08.003. Epub 2020 Aug 27.
Clinical trials evaluating universal PARP inhibitor (PARPi) frontline maintenance therapy for advanced stage ovarian cancer have reported progression-free survival (PFS) benefit. It is unclear whether PARPi maintenance therapy will universally enhance value (clinical benefits relative to cost of delivery). We compared a "PARPi-for-all" to a biomarker-directed frontline maintenance therapy approach as a value-based care strategy.
The cost of two frontline PARPi maintenance strategies, PARPi-for-all and biomarker-directed maintenance, was compared using modified Markov decision models simulating the study designs of the PRIMA, VELIA, and, PAOLA-1 trials. Outcomes of interest included overall costs and incremental cost-effectiveness ratios (ICERs) reported in US dollars per quality adjusted progression-free life-year (QA-PFY) gained.
PARPi-for-all was more costly and provided greater PFS benefit than a biomarker-directed strategy for each trial. The mean cost per patient for the PARPi-for-all strategy was $166,269, $286,715, and $366,506 for the PRIMA, VELIA, and PAOLA-1 models, respectively. For the biomarker-directed strategy, the mean cost per patient was $98,188, $167,334, and $260,671 for the PRIMA, VELIA, and PAOLA-1 models. ICERs of PARPi-for-all compared to biomarker-directed maintenance were: $593,250/QA-PFY (PRIMA), $1,512,495/QA-PFY (VELIA), and $3,347,915/QA-PFY (PAOLA-1). At current drug pricing, there is no PFS improvement in a biomarker negative cohort that would make PARPi-for-all cost-effective compared to biomarker-directed maintenance.
This study highlights the high costs of universal PARPi maintenance treatment, compared with a biomarker-directed PARPi strategy. Maintenance therapy in the front-line setting should be reserved for those with germline or somatic HRD mutations until the cost of therapy is significantly reduced.
评估广泛应用聚腺苷二磷酸核糖聚合酶抑制剂（PARPi）作为晚期卵巢癌一线维持治疗的临床试验报告了无进展生存期（PFS）获益。目前尚不清楚 PARPi 维持治疗是否会普遍提高价值（相对于治疗成本的临床获益）。我们比较了一种“PARPi 适用于所有”与生物标志物指导的一线维持治疗方法作为基于价值的护理策略。
使用改良的 Markov 决策模型比较两种一线 PARPi 维持策略（PARPi 适用于所有和生物标志物指导维持）的成本，该模型模拟了 PRIMA、VELIA 和 PAOLA-1 试验的研究设计。感兴趣的结果包括以每质量调整无进展生存期（QA-PFY）获得美元为单位的总费用和增量成本效益比（ICER）。
与生物标志物指导策略相比，PARPi 适用于所有策略在每个试验中都更昂贵，但提供了更大的 PFS 获益。PARPi 适用于所有策略的每位患者平均成本分别为 PRIMA、VELIA 和 PAOLA-1 模型的 166269 美元、286715 美元和 366506 美元。对于生物标志物指导策略，每位患者的平均成本分别为 PRIMA、VELIA 和 PAOLA-1 模型的 98188 美元、167334 美元和 260671 美元。PARPi 适用于所有策略与生物标志物指导维持的 ICER 分别为：PRIMA 模型为 593250 美元/QA-PFY、VELIA 模型为 1512495 美元/QA-PFY 和 PAOLA-1 模型为 3347915 美元/QA-PFY。在当前药物定价下，对于生物标志物阴性队列，PARPi 适用于所有的 PFS 改善不会使其具有成本效益，除非治疗成本显著降低。
本研究强调了与生物标志物指导的 PARPi 策略相比，广泛应用 PARPi 维持治疗的高成本。在一线治疗环境中，维持治疗应保留给有生殖系或体细胞 HRD 突变的患者，直到治疗成本显著降低。
