BACKGROUND AND OBJECTIVE Over the past 5 years, adjuvant treatment options for surgically resected stage III melanoma have expanded with the introduction of several novel immune checkpoint inhibitors and targeted therapies. Pembrolizumab, a programmed cell death protein 1 inhibitor, received US Food and Drug Administration approval in 2019 for resected high-risk stage III melanoma based on significantly longer recurrence-free survival versus placebo. This study evaluated the cost-effectiveness of pembrolizumab versus other adjuvant treatment strategies for resected high-risk stage III melanoma from a US health system perspective. METHODS A Markov cohort-level model with four states (recurrence-free, locoregional recurrence, distant metastases, death) estimated costs and quality-adjusted life-years (QALYs) for pembrolizumab versus routine observation and other adjuvant comparators: ipilimumab in the overall population; and dabrafenib + trametinib in the BRAF-mutation positive (BRAF+) subgroup. Transition probabilities starting from recurrence-free were estimated through parametric multi-state modeling based on phase 3 KEYNOTE-054 (NCT02362594) trial data for pembrolizumab and observation, and network meta-analyses for other comparators. Post-recurrence transitions were modeled based on electronic medical records data and trials in advanced/metastatic melanoma. Utilities were derived using quality-of-life data from KEYNOTE-054 and literature. Costs of treatment, adverse events, disease management, and terminal care were included. RESULTS Over a lifetime, pembrolizumab, ipilimumab, and observation were associated with QALYs of 9.24, 7.09, and 5.95 and total costs of $511,290, $992,721, and $461,422, respectively (2019 US dollars). Pembrolizumab was thus dominant (less costly, more effective) versus ipilimumab, with an incremental cost-effectiveness ratio of $15,155/QALY versus observation. In the BRAF+ subgroup, pembrolizumab dominated dabrafenib + trametinib and observation, decreasing costs by $62,776 and $11,250 and increasing QALYs by 0.93 and 3.10 versus these comparators, respectively. Results were robust in deterministic and probabilistic sensitivity analyses. CONCLUSIONS As adjuvant treatment for resected stage III melanoma, pembrolizumab was found to be dominant and therefore cost-effective compared with the active comparators ipilimumab and dabrafenib + trametinib. Pembrolizumab increased costs relative to observation in the overall population, with sufficient incremental benefit to be considered cost-effective based on typical willingness-to-pay thresholds.

中文翻译：

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派姆单抗与其他辅助治疗策略在美国切除的高危III期黑色素瘤的经济评价。

背景和目的在过去的5年中，随着外科切除的III期黑色素瘤的辅助治疗选择的增加，引入了几种新型的免疫检查点抑制剂和靶向疗法。Pembrolizumab是一种程序性细胞死亡蛋白1抑制剂，由于与安慰剂相比具有更长的无复发生存期，因此于2019年获得美国食品和药物管理局批准用于切除的高危III期黑色素瘤。这项研究从美国卫生系统的角度评估了Pembrolizumab与其他辅助治疗策略在切除高危III期黑色素瘤中的成本效益。方法具有四个状态的Markov队列水平模型（无复发，局部复发，远处转移，派姆单抗与常规观察和其他辅助比较者的估计成本和质量调整生命年（QALYs）：总人群中的ipilimumab；和BRAF突变阳性（BRAF +）亚组中的dabrafenib +曲美替尼。基于参数3的KEYNOTE-054（NCT02362594）派姆单抗和观察数据以及针对其他比较器的网络荟萃分析，通过参数多状态建模，估算了从无复发开始的转移概率。基于电子病历数据和晚期/转移性黑素瘤的试验对复发后的转移进行建模。实用程序是使用KEYNOTE-054和文献中的生活质量数据得出的。包括治疗费用，不良事件，疾病管理和最终护理费用。结果pembrolizumab，ipilimumab，与观察值相关的QALY为9.24、7.09和5.95，总成本分别为511,290美元，992,721美元和461,422美元（2019年美元）。因此，与依匹莫单抗相比，派姆单抗占主导地位（成本更低，更有效），与观察值相比，成本效益比增加了15155美元/ QALY。在BRAF +亚组中，pembrolizumab占主导地位的达拉非尼+曲美替尼和观察，与这些比较者相比，成本分别降低了62,776美元和11,250美元，并且QALY增加了0.93和3.10。结果在确定性和概率敏感性分析中是可靠的。结论作为切除的III期黑色素瘤的辅助治疗，与主动比较剂ipilimumab和dabrafenib +曲美替尼相比，pembrolizumab是主要治疗药物，因此具有成本效益。