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Abstract：
BACKGROUND: Patients with locally advanced/metastatic urothelial cancer have been conventionally treated with platinum-based chemotherapy. Recently, numerous new treatments have been proposed to improve overall survival (OS) and reduce adverse effects, but no direct head-to-head comparisons among these agents are available.
METHODS: The treatments evaluated in our analyses included (a) monotherapy with immune checkpoint inhibitors (ICI); (b) combinations of an ICI with chemotherapy; and (c) combinations of an ICI with other drugs. Using OS as the endpoint, a series of indirect comparisons were performed to rank the most effective regimens against both chemotherapy and each other. Our analysis was based on the application of an artificial intelligence software program (IPDfromKM method) that reconstructs individual patient data from the information reported in the graphs of Kaplan-Meier curves.
RESULTS: A total of five studies published in six articles were included. In our main analysis, nivolumab plus chemotherapy showed better OS compared to chemotherapy (HR = 0.70, 95% CI: 0.59-0.82), while durvalumab plus tremelimumab showed no OS benefit (HR = 0.95, 95% CI 0.82-1.11). More interestingly, enfortumab vedotin plus pembrolizumab significantly prolonged OS compared to both chemotherapy alone (HR = 0.53, 95% CI 0.45-0.63) and nivolumab plus chemotherapy (HR = 0.76, 95% CI 0.60-0.97).
CONCLUSIONS: Among new treatments for locally advanced and metastatic urothelial cancer, enfortumab vedotin plus pembrolizumab showed the best efficacy in terms of OS. Our results support the use of this combination as a first-line treatment in this setting.
METHODS: The treatments evaluated in our analyses included (a) monotherapy with immune checkpoint inhibitors (ICI); (b) combinations of an ICI with chemotherapy; and (c) combinations of an ICI with other drugs. Using OS as the endpoint, a series of indirect comparisons were performed to rank the most effective regimens against both chemotherapy and each other. Our analysis was based on the application of an artificial intelligence software program (IPDfromKM method) that reconstructs individual patient data from the information reported in the graphs of Kaplan-Meier curves.
RESULTS: A total of five studies published in six articles were included. In our main analysis, nivolumab plus chemotherapy showed better OS compared to chemotherapy (HR = 0.70, 95% CI: 0.59-0.82), while durvalumab plus tremelimumab showed no OS benefit (HR = 0.95, 95% CI 0.82-1.11). More interestingly, enfortumab vedotin plus pembrolizumab significantly prolonged OS compared to both chemotherapy alone (HR = 0.53, 95% CI 0.45-0.63) and nivolumab plus chemotherapy (HR = 0.76, 95% CI 0.60-0.97).
CONCLUSIONS: Among new treatments for locally advanced and metastatic urothelial cancer, enfortumab vedotin plus pembrolizumab showed the best efficacy in terms of OS. Our results support the use of this combination as a first-line treatment in this setting.
摘要：
背景：患有局部晚期/转移性尿路上皮癌的患者已常规使用基于铂的化学疗法进行治疗。最近,已经提出了许多新的治疗方法来提高总生存率（OS）并减少不良反应，但这些药物之间没有直接的头对头比较。
方法：在我们的分析中评估的治疗包括（a）免疫检查点抑制剂（ICI）的单一疗法；（b）ICI与化疗的组合；和（c）ICI与其他药物的组合。使用操作系统作为端点，我们进行了一系列间接比较,对最有效的化疗方案和其他方案进行排名.我们的分析基于人工智能软件程序（IPDfromKM方法）的应用，该程序根据Kaplan-Meier曲线中报告的信息重建了个体患者数据。
结果：共纳入了发表在六篇文章中的五项研究。在我们的主要分析中，与化疗相比，纳武单抗联合化疗显示出更好的OS（HR=0.70，95％CI：0.59-0.82），而durvalumab联合tremelimumab无OS获益(HR=0.95,95%CI0.82-1.11).更有趣的是，与单独化疗(HR=0.53,95%CI0.45-0.63)和nivolumab联合化疗(HR=0.76,95%CI0.60-0.97)相比,enfortumabvedotin联合派姆单抗显著延长OS.
结论：在局部晚期和转移性尿路上皮癌的新疗法中，就OS而言，enfortumabvedotin联合pembrolizumab显示出最佳疗效。我们的结果支持在这种情况下使用这种组合作为一线治疗。
方法：在我们的分析中评估的治疗包括（a）免疫检查点抑制剂（ICI）的单一疗法；（b）ICI与化疗的组合；和（c）ICI与其他药物的组合。使用操作系统作为端点，我们进行了一系列间接比较,对最有效的化疗方案和其他方案进行排名.我们的分析基于人工智能软件程序（IPDfromKM方法）的应用，该程序根据Kaplan-Meier曲线中报告的信息重建了个体患者数据。
结果：共纳入了发表在六篇文章中的五项研究。在我们的主要分析中，与化疗相比，纳武单抗联合化疗显示出更好的OS（HR=0.70，95％CI：0.59-0.82），而durvalumab联合tremelimumab无OS获益(HR=0.95,95%CI0.82-1.11).更有趣的是，与单独化疗(HR=0.53,95%CI0.45-0.63)和nivolumab联合化疗(HR=0.76,95%CI0.60-0.97)相比,enfortumabvedotin联合派姆单抗显著延长OS.
结论：在局部晚期和转移性尿路上皮癌的新疗法中，就OS而言，enfortumabvedotin联合pembrolizumab显示出最佳疗效。我们的结果支持在这种情况下使用这种组合作为一线治疗。
