Cisplatin-based chemotherapy is currently the first-line standard of care for patients with metastatic urothelial cancer (mUC); however, up to 50% of patients are ineligible for cisplatin, necessitating alternative treatment options. Immune checkpoint inhibitors have been shown to be effective in cisplatin-ineligible patients. However, despite advances in the first-line setting, the prognosis remains poor, and challenges persist in selecting optimal therapies, treatment sequences and combination regimens. Maintenance therapy with avelumab revealed improved overall (OS) and progression-free survival (PFS) compared with best supportive care alone in patients with platinum-responsive mUC. Antibody–drug conjugates and targeted therapy with fibroblast growth factor receptor (FGFR) inhibitors have shown promise in selected patients, particularly in patients with metastatic disease that has progressed despite platinum-based chemotherapy. At the European Society of Medical Oncology Congress in 2023, groundbreaking results were presented from two phase III trials, EV-302/KEYNOTE-A39 and CheckMate 901, focusing on previously untreated mUC. In the former, the combination of enfortumab vedotin and pembrolizumab showed significant improvements in OS, PFS and overall response rate compared with chemotherapy alone; the combination of nivolumab with gemcitabine–cisplatin chemotherapy demonstrated a significant extension in median OS, PFS and overall response rate compared with chemotherapy alone. In addition, erdafitinib therapy resulted in significantly longer OS than chemotherapy among patients with mUC and FGFR alterations after previous treatment with immune checkpoint inhibitors. This comprehensive summary of the current treatment landscape for mUC incorporates clinical trial evidence and discussion of agents that are currently under investigation to provide support for clinical decision making and understanding of future therapeutic approaches.

基于顺铂的化疗目前是转移性尿路上皮癌（mUC）患者的一线治疗标准；然而，高达 50% 的患者不适合使用顺铂，因此需要替代治疗方案。免疫检查点抑制剂已被证明对不适合顺铂的患者有效。然而，尽管一线治疗取得了进展，但预后仍然很差，并且在选择最佳疗法、治疗顺序和联合方案方面仍然存在挑战。与单独最佳支持治疗相比，avelumab 维持治疗显示铂类反应性 mUC 患者的总生存期 (OS) 和无进展生存期 (PFS) 有所改善。抗体药物偶联物和成纤维细胞生长因子受体 (FGFR) 抑制剂的靶向治疗在某些患者中显示出了希望，特别是对于尽管接受铂类化疗但仍出现进展的转移性疾病患者。在 2023 年的欧洲肿瘤内科学会大会上，公布了两项 III 期试验 EV-302/KEYNOTE-A39 和 CheckMate 901 的突破性结果，重点关注先前未经治疗的 mUC。前者与单独化疗相比，enfortumab vedotin 和 pembrolizumab 联合显示 OS、PFS 和总体缓解率显着改善；与单独化疗相比，纳武单抗与吉西他滨-顺铂化疗的组合显示中位 OS、PFS 和总体缓解率显着延长。此外，对于既往接受免疫检查点抑制剂治疗后出现 mUC 和 FGFR 改变的患者，erdafitinib 疗法比化疗显着延长了 OS。 这份对 mUC 当前治疗前景的全面总结结合了临床试验证据和目前正在研究的药物的讨论，为临床决策和对未来治疗方法的理解提供支持。