Sherrow Christopher, Attwood Kristopher, Zhou Kehua, Mukherjee Sarbajit, Iyer Renuka, Fountzilas Christos
Department of Pharmacy, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Liver Cancer. 2020 Sep;9(5):549-562. doi: 10.1159/000508485. Epub 2020 Aug 12.
Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide and carries a poor prognosis. Historically, sorafenib was the only available systemic treatment for advanced HCC. However, in recent years, 6 new treatments have been approved by the US Food and Drug Administration (FDA): regorafenib, lenvatinib, cabozantinib, pembrolizumab, ramucirumab, and nivolumab. Data are lacking regarding the most appropriate sequencing pathway for these agents. Our objective was to conduct a comprehensive cost effectiveness analysis (CEA) of different 1st- and 2nd-line treatment pathways for HCC reflecting all new drug approvals, and then use our data to provide guidance for clinicians on which pathway is the most cost-effective.
Markov models were used to evaluate the cost effectiveness of 8 different 1st- and 2nd-line treatment sequences. The model allowed for 9 possible states. Cost effectiveness ratios (CER) and incremental CER (ICER) were calculated to compare costs between different pathways and against a willingness-to-pay (WTP) threshold. Efficacy and toxicity data were extracted from the landmark trials for each agent. All agents except ramucirumab were included. The cost of each agent was based on the wholesale acquisition cost (WAC) in USD as of June 2019. Monte-Carlo methods were used to simulate the experience of 1,000,000 patients per treatment sequence for a 12-month period.
The pathway with the lowest CER was sorafenib, followed by pembrolizumab (USD 227,741.03/quality-adjusted life year [QALY]). ICER analysis supported implementing 2nd-line pembrolizumab-based pathways at a higher WTP threshold of 300,000/quality-adjusted life year. Sensitivity analysis did not substantially change these results.
The most cost-effective strategy was 1st-line tyrosine kinase inhibitor therapy followed by 2nd-line immunotherapy. All pathways exceeded a commonly accepted WTP of USD 100-150,000/QALY. Our preliminary results warrant further studies to best inform real-world practices.
肝细胞癌（HCC）是全球最常见的肝癌形式，预后较差。历史上，索拉非尼是晚期HCC唯一可用的全身治疗药物。然而，近年来，美国食品药品监督管理局（FDA）已批准了6种新的治疗药物：瑞戈非尼、仑伐替尼、卡博替尼、帕博利珠单抗、雷莫西尤单抗和纳武利尤单抗。关于这些药物最合适的用药顺序尚缺乏相关数据。我们的目标是对反映所有新药获批情况的HCC不同一线和二线治疗方案进行全面的成本效益分析（CEA），然后利用我们的数据为临床医生提供指导，指出哪种方案最具成本效益。
采用马尔可夫模型评估8种不同一线和二线治疗顺序的成本效益。该模型考虑了9种可能的状态。计算成本效益比（CER）和增量成本效益比（ICER），以比较不同方案之间的成本，并与支付意愿（WTP）阈值进行对比。疗效和毒性数据从每种药物的标志性试验中提取。除雷莫西尤单抗外，所有药物均被纳入分析。每种药物的成本基于截至2019年6月的美元批发采购成本（WAC）。采用蒙特卡洛方法模拟每个治疗顺序下100万名患者12个月的治疗情况。
CER最低的方案是索拉非尼，其次是帕博利珠单抗（227,741.03美元/质量调整生命年[QALY]）。ICER分析支持在更高的WTP阈值（300,000美元/质量调整生命年）下实施基于二线帕博利珠单抗的方案。敏感性分析并未显著改变这些结果。
最具成本效益的策略是一线酪氨酸激酶抑制剂治疗，随后进行二线免疫治疗。所有方案均超过了100,000 - 150,000美元/QALY这一普遍接受的WTP。我们的初步结果值得进一步研究，以便为实际临床实践提供最佳参考。
