Gasperoni Lorenzo, Del Bono Luna, Ossato Andrea, Giunta Emilio Francesco, Messori Andrea, Damuzzo Vera
Oncological Pharmacy Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.
Azienda Ospedaliera Universitaria Pisana, 56100 Pisa, Italy.
Cancers (Basel). 2024 Jun 29;16(13):2400. doi: 10.3390/cancers16132400.
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.
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.
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).
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.
局部晚期/转移性尿路上皮癌患者传统上接受铂类化疗。最近，人们提出了许多新的治疗方法以提高总生存期（OS）并减少不良反应，但这些药物之间尚无直接的头对头比较。
我们分析中评估的治疗方法包括：（a）免疫检查点抑制剂（ICI）单药治疗；（b）ICI与化疗联合；（c）ICI与其他药物联合。以OS为终点，进行了一系列间接比较，以对针对化疗以及彼此之间最有效的治疗方案进行排名。我们的分析基于一个人工智能软件程序（IPDfromKM方法）的应用，该程序从Kaplan-Meier曲线图表中报告的信息重建个体患者数据。
总共纳入了六篇文章中发表的五项研究。在我们的主要分析中，纳武利尤单抗联合化疗与化疗相比显示出更好的OS（HR = 0.70，95%CI：0.59 - 0.82），而度伐利尤单抗联合曲美木单抗未显示出OS获益（HR = 0.95，95%CI 0.82 - 1.11）。更有趣的是，与单纯化疗（HR = 0.53，95%CI 0.45 - 0.63）和纳武利尤单抗联合化疗（HR = 0.76，95%CI 0.60 - 0.97）相比，恩杂鲁胺联合帕博利珠单抗显著延长了OS。
在局部晚期和转移性尿路上皮癌的新治疗方法中，恩杂鲁胺联合帕博利珠单抗在OS方面显示出最佳疗效。我们的结果支持在这种情况下将这种联合作为一线治疗方法使用。
