Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma
Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma
复制标题
DOI：
10.1200/jco.2016.69.6336
复制
发表时间：
2017-04-10
影响因子：
45.3
通讯作者：
Flowers, Christopher R.
中科院分区：
文献类型：
--
作者：
Kohn, Christine G.;Zeichner, Simon B.;Flowers, Christopher R.
目的：IV期转移性黑色素瘤患者的5年相对生存率估计只有17%。最近美国食品和药物管理局批准的免疫检查点药物-pembrolizumab（PEM），nivolumab（NIVO）和ipilumumab（IPI）的随机对照试验表明改善了患者结局，但BRAF野生型转移性黑色素瘤患者的最佳治疗顺序仍不清楚。为了告知政策制定者这些治疗的价值，我们开发了一个马尔可夫模型来比较用于治疗晚期黑素瘤的测序新药物的不同策略的成本效益。材料和方法我们开发了马尔可夫模型，通过使用美国付款人的观点和寿命范围来估计成本一线NIVO、IPI、NIVO + IPI、PEM每2周一次和PEM每3周一次治疗序列的平均寿命（2016美元）和质量调整生命年（Qs）。健康状态定义为初始治疗、第一次和第二次进展以及死亡。停药率、不良事件发生率、疾病进展率和从随机III期试验中获得的死亡率用于确定状态之间转换的可能性。进行了确定性和概率敏感性分析，以评估模型的不确定性。ResultsPEM每3周，其次是二线IPI是更有效的和更便宜的比达卡巴嗪其次是IPI然后NIVO，或IPI其次是NIVO。与一线达卡巴嗪治疗策略相比，NIVO + IPI+卡铂+紫杉醇化疗的增量成本效果比为90，871美元/QALY，NIVO + IPI+卡铂+紫杉醇化疗的增量成本效果比为198，867美元/QALY。每3周一次的一线PEM，随后是二线IPI或一线NIVO，随后是二线IPI，是转移性黑色素瘤最具成本效益的基于免疫的治疗策略。(C)2017年美国临床肿瘤学会
PurposePatients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)-demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma.Materials and MethodsWe developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty.ResultsPEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $ 198,867/QALY.ConclusionFor patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective, immune-based treatment strategies for metastatic melanoma. (C) 2017 by American Society of Clinical Oncology