Division of Gynecologic Oncology, University of California, Irvine, Orange, CA, USA.
School of Business, Wake Forest University, Winston-Salem, NC, USA.
Gynecol Oncol. 2020 May;157(2):500-507. doi: 10.1016/j.ygyno.2020.02.030. Epub 2020 Mar 13.
Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2-mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease.
Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non‑platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations.
Non‑platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3-3.5× times greater than intravenous non‑platinum-based regimens.
High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care.
奥拉帕利于 2014 年 12 月 19 日被美国食品和药物管理局批准为第 4 线（及以上）治疗方法，适用于携带胚系 BRCA1/2 突变的患者；鲁卡帕利于 2016 年 12 月 19 日被批准为第 3 线（及以上）治疗方法，适用于携带胚系或体细胞 BRCA1/2 突变的复发性疾病。2019 年 10 月 23 日，尼拉帕利被批准用于治疗携带 BRCA1/2 或其他同源重组修复基因有害突变的女性，这些女性已接受了三种或更多的既往治疗方案。我们比较了 PARPi(s)与用于铂耐药疾病的静脉内方案的成本效益。
监管试验的中位无进展生存期 (PFS) 和毒性数据被纳入模型，该模型使患者通过反应、血液学并发症、非血液学并发症、进展和死亡进行过渡。使用 TreeAge Pro 2017，将每种 PARPi(s) 分别与非铂类和贝伐珠单抗联合方案进行比较。使用 2017 年医疗保险数据估计 IV 药物、管理毒性、输注和支持性护理的成本。计算增量成本效益比 (ICER)，并以质量调整生命月报告铂耐药人群的 PFS。
与贝伐珠单抗联合方案（PFS 月 12187 美元）、尼拉帕利（PFS 月 18970 美元）、奥拉帕利（PFS 月 16327 美元）和鲁卡帕利（PFS 月 16637 美元）相比，非铂类静脉内化疗是最具成本效益的（PFS 月 6412 美元）。PARPi(s) 的 ICER 是静脉内非铂类方案的 3-3.5 倍。
口服 PARPi(s) 的高成本并未因输注成本和管理毒性而减轻或平衡，而这些毒性通常与较低的反应和较短的中位 PFS 相关。用新型疗法的适度临床获益来平衡成本仍然是一个问题，并且可能会扩大那些获得有限医疗资源的人的差距。
