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

转移性尿路上皮癌（mUCa）因频繁的干预和高昂的随访费用，成为每例患者治疗成本最高的癌症之一。我们研究了一线治疗方案的成本-效果，发现enfortumab vedotin联合pembrolizumab（EV + P）以及吉西他滨/顺铂联合nivolumab在总生存期（OS）方面优于标准治疗（SoC；吉西他滨/顺铂）。我们基于支付者视角，利用第三期临床试验Checkmate-901和EV302/Keynote-A39的数据，建立了Markov模型，通过蒙特卡洛模拟确定德国和美国的最优治疗方案，并比较了不同意愿支付阈值下各方案的增量成本-效果比（ICER）。在终生分析中，SoC、吉西他滨/顺铂+nivolumab和EV+P的平均成本分别为163,424欧元（美国：458,006美元）、206,853欧元（美国：597,802美元）和401,170欧元（美国：1,228,455美元），获得的质量调整生命年（QALYs）分别为1.21、1.71和2.31。各新策略的ICER为87,340欧元（美国：281,142美元；吉西他滨/顺铂+nivolumab）和216,140欧元（美国：700,448美元；EV+P）。在常用的€/$10万WTP阈值下，吉西他滨/顺铂+nivolumab在德国为最优策略，而EV+P需要降价46%（美国：82%）才能具有成本效益。EV+P带来的QALYs几乎翻倍，但目前的成本在严格的社会经济角度下可能不合理。尽管其肿瘤学获益较低，但考虑到成本效益，吉西他滨/顺铂+nivolumab在欧洲仍是首选一线方案。未来，明确个体风险因素对于优化治疗反应和控制成本至关重要。本报告分析了转移性尿路上皮癌新兴治疗方法的成本-效果，发现enfortumab vedotin+pembrolizumab最具疗效，但成本最高。纯粹从社会经济角度考虑，吉西他滨/顺铂联合nivolumab是较优的替代方案，特别是在德国。

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.