Casabianca Paul, Massetti Marc, Cotte François-Emery, Moreau Romain, Kassahun Sarah, Singh Prianka, Kim Inkyu, Gaudin Anne-Françoise, Piessen Guillaume, Leleu Henri
Health Economics & Outcomes Research, Bristol Myers Squibb France, 92500, Rueil-Malmaison, France.
Health Economics & Outcomes Research, Public Health Expertise, 75004, Paris, France.
Pharmacoecon Open. 2024 Sep;8(5):689-699. doi: 10.1007/s41669-024-00500-y. Epub 2024 Jul 4.
Esophageal and gastroesophageal junction cancer (EC/GEJC) is a poor prognosis disease with a high risk of recurrence even in patients curatively resected. Adjuvant nivolumab is currently used for patients with completely resected (R0) EC/GEJC who have residual pathologic disease following prior neoadjuvant chemoradiotherapy. This study aimed to determine the cost effectiveness of nivolumab in this indication in France according to the collective perspective excluding indirect costs.
A simplified four-health-state semi-Markov model was developed to model EC/GEJC patients who have residual disease after neoadjuvant chemoradiotherapy followed by R0 over a 15-year time horizon, comparing adjuvant nivolumab versus surveillance, which was the recommended French clinical practice before immunotherapy arrival. Time-to-recurrence (TTR) from CheckMate 577 was used to inform transition from disease-free to post-recurrence health state; patients who recurred were split according to the distribution of type of recurrence observed during the trial. Post-recurrence survival (PRS) according to the type of recurrence was derived from a real-world registry.
Adjuvant treatment with nivolumab led to an incremental survival gain of 1.19 years (+ 34%), mostly in the disease-free state, an incremental cost of €48,634 and QALY of 0.98 resulting in an incremental cost-utility ratio (ICUR) of €49,572/QALY with limited uncertainty. 'Cure assumption' at 5 years had an important impact on the results (€41,115/QALY; - 17%), as that tends to increase life-years and QALYs while costs remain the same. Probabilistic sensitivity analyses confirmed reference ICUR (€52,542/QALY) with 80% probability of nivolumab being cost effective at a willingness-to-pay threshold of €75,000/QALY.
Our analysis suggests that adjuvant nivolumab is cost effective in the treatment of EC/GEJC patients who have residual disease after neoadjuvant CRT followed by R0 resection. Compared with previously evaluated cost-effectiveness analyses for other immune-checkpoint inhibitors indicated in metastatic settings, ICUR appears particularly low in this early setting thanks to the important impact on health outcomes and capped treatment duration.
食管癌和胃食管交界癌（EC/GEJC）预后较差，即使是接受了根治性切除的患者，复发风险也很高。目前，辅助性纳武单抗用于接受过新辅助放化疗后仍有残留病理疾病的完全切除（R0）的EC/GEJC患者。本研究旨在从集体角度（不包括间接成本）确定纳武单抗在法国该适应症中的成本效益。
开发了一个简化的四健康状态半马尔可夫模型，对新辅助放化疗后有残留疾病且随后进行R0切除的EC/GEJC患者进行为期15年的建模，比较辅助性纳武单抗与监测（免疫疗法出现之前法国推荐的临床实践）。来自CheckMate 577试验的复发时间（TTR）用于确定从无病状态到复发后健康状态的转变；复发患者根据试验期间观察到的复发类型分布进行划分。复发后生存（PRS）根据复发类型来自一个真实世界的登记处。
纳武单抗辅助治疗导致生存增量获益1.19年（+34%），主要在无病状态，增量成本为48,634欧元，质量调整生命年（QALY）为0.98，导致增量成本效用比（ICUR）为49,572欧元/QALY，不确定性有限。5年时的“治愈假设”对结果有重要影响（41,115欧元/QALY；-17%），因为这往往会增加生命年和QALY，而成本保持不变。概率敏感性分析证实了参考ICUR（52,542欧元/QALY），纳武单抗在支付意愿阈值为75,000欧元/QALY时有80%的概率具有成本效益。
我们的分析表明，辅助性纳武单抗在治疗新辅助放化疗后有残留疾病且随后进行R0切除的EC/GEJC患者中具有成本效益。与先前评估的转移性环境中其他免疫检查点抑制剂的成本效益分析相比，由于对健康结果的重要影响和有限的治疗持续时间，在这种早期环境中ICUR显得特别低。
