基于Checkmate-901和EV302/Keynote-A39的转移性尿路上皮癌新治疗策略的成本-效益分析

转移性尿路上皮癌（mUCa）由于频繁的干预和昂贵的随访，成为每位患者治疗成本最高的癌症之一。我们对一线治疗方案进行了成本-效益分析，包括恩福昔单抗（enfortumab vedotin）联合派姆单抗（pembrolizumab, EV + P）以及吉西他滨/顺铂（gemcitabine/cisplatin）联合尼洛单抗（nivolumab），它们在总体存活（OS）方面均优于标准治疗（SoC；吉西他滨/顺铂）。我们建立了一个从支付者角度出发的马尔可夫模型，基于第三阶段临床试验Checkmate-901和EV302/Keynote-A39的临床数据。利用蒙特卡洛模拟确定在德国和美国的社会经济角度下的最优治疗方案，并在不同意愿支付阈值（WTP）下比较各方案的增量成本-效益比（ICER）。在终身视角下，标准治疗、吉西他滨/顺铂+尼洛单抗和EV + P的平均成本分别为163,424欧元（美国：$458,006）、206,853欧元（美国：$597,802）和401,170欧元（美国：$1,228,455），获得的质量调整生命年（QALYs）分别为1.21、1.71和2.31。新策略的ICER为87,340欧元（美国：$281,142；吉西他滨/顺铂+尼洛单抗）和216,140欧元（美国：$700,448；EV + P）。在常用的WTP阈值€/$100,000下，吉西他滨/顺铂+尼洛单抗在德国为最优策略，而EV + P若价格降低46%（美国降低82%）则具有成本效益。相比目前的标准治疗，EV + P的QALYs几乎翻倍，但从严格的社会经济角度看，当前成本可能尚难完全合理。尽管其肿瘤学益处较低，吉西他滨/顺铂+尼洛单抗仍应作为一线治疗考虑，特别是在欧洲，以实现良好的成本效益。未来应结合个体风险因素，优化治疗反应和成本。本报告分析了转移性尿路上皮癌新兴治疗方案的成本效益，发现恩福昔单抗联合派姆单抗是最有效的方案，但也是成本最高的。从纯粹的社会经济角度来看，吉西他滨/顺铂与尼洛单抗的组合在德国具有较好的成本效益。

Metastatic urothelial carcinoma (mUCa) ranks as the costliest cancer to treat per patient due to frequent interventions and expensive follow-ups. Investigating first-line therapies, combinations such as enfortumab vedotin + pembrolizumab (EV + P) and gemcitabine/cisplatin + nivolumab exhibit significant overall survival benefits compared with the standard treatment (SoC; gemcitabine/cisplatin). Here, we conducted a cost-effectiveness analysis for mUCa.We developed a Markov model from a payer perspective, filtering clinical data from the phase 3 Checkmate-901 and EV302/Keynote-A39 trials. Monte Carlo simulation was used to identify the optimal treatment from a socioeconomic perspective in Germany and the USA. Finally, we compared the incremental cost-effectiveness ratio (ICER) of each modality at different willingness-to-pay (WTP) thresholds.At a lifetime horizon, SoC, gemcitabine/cisplatin + nivolumab, and EV + P were associated with average costs of €163 424 (USA: $458 006), €206 853 (USA: $597 802), and €401 170 (USA: $1 228 455), and gained quality-adjusted life years (QALYs) of 1.21, 1.71, and 2.31, respectively. The ICERs of the newer strategies were €87 340 (USA: $281 142; gemcitabine/cisplatin + nivolumab) and €216 140 (USA: $700 448; EV + P). At a commonly used WTP threshold of €/$100 000, gemcitabine/cisplatin + nivolumab would be the optimal strategy in Germany, while EV + P would require a price reduction of 46% (USA: 82%) to be cost effective.QALYs nearly double with EV + P compared with the current SoC; yet, current costs may not be justified from a strict socioeconomic perspective. Despite its lower oncological benefit, gemcitabine/cisplatin + nivolumab should be considered for first-line therapy due to favorable cost effectiveness, especially in Europe. Establishing individual risk factors is essential for optimizing therapeutic response and treatment costs in the future.This report presents a cost-effectiveness analysis of emerging treatment options for metastatic urothelial carcinoma. The combination of enfortumab vedotin + pembrolizumab emerged as the most effective treatment; however, it also proved to be the costliest. From a purely socioeconomic standpoint, the combination of gemcitabine/cisplatin and nivolumab represents a cost-effective alternative at least in Germany.