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Abstract：
The JAVELIN Bladder 100 phase III trial led to the incorporation of avelumab first-line (1L) maintenance treatment into international guidelines as a standard of care for patients with advanced urothelial carcinoma (UC) without progression after 1L platinum-based chemotherapy. JAVELIN Bladder 100 showed that avelumab 1L maintenance significantly prolonged overall survival (OS) and progression-free survival in this population compared with a \'watch-and-wait\' approach. The aim of this manuscript is to review clinical studies of avelumab 1L maintenance in patients with advanced UC, including long-term efficacy and safety data from JAVELIN Bladder 100, subgroup analyses in clinically relevant subpopulations, and \'real-world\' data obtained outside of clinical trials, providing a comprehensive resource to support patient management. Extended follow-up from JAVELIN Bladder 100 has shown that avelumab provides a long-term efficacy benefit, with a median OS of 23.8 months measured from start of maintenance treatment, and 29.7 months measured from start of 1L chemotherapy. Longer OS was observed across subgroups, including patients who received 1L cisplatin + gemcitabine, patients who received four or six cycles of 1L chemotherapy, and patients with complete response, partial response, or stable disease as best response to 1L induction chemotherapy. No new safety signals were seen in patients who received ≥1 year of avelumab treatment, and toxicity was similar in those who had received cisplatin or carboplatin with gemcitabine. Other clinical datasets, including noninterventional studies conducted in Europe, USA, and Asia, have confirmed the efficacy of avelumab 1L maintenance. Potential subsequent treatment options after avelumab maintenance include antibody-drug conjugates (enfortumab vedotin or sacituzumab govitecan), erdafitinib in biomarker-selected patients, platinum rechallenge in suitable patients, nonplatinum chemotherapy, and clinical trial participation; however, evidence to determine optimal treatment sequences is needed. Ongoing trials of avelumab-based combination regimens as maintenance treatment have the potential to evolve the treatment landscape for patients with advanced UC.
摘要：
JAVELIN膀胱100III期试验导致将avelumab一线（1L）维持治疗纳入国际指南，作为晚期尿路上皮癌（UC）患者在1L铂类化疗后无进展的护理标准。JAVELIN膀胱100显示，与“观察并等待”方法相比，该人群的avelumab1L维持显着延长了总生存期（OS）和无进展生存期。本手稿的目的是回顾阿维鲁单抗1L维持晚期UC患者的临床研究，包括JAVELIN膀胱100的长期疗效和安全性数据，临床相关亚群的亚组分析，以及在临床试验之外获得的“真实世界”数据，提供全面的资源来支持患者管理。JAVELIN膀胱100的长期随访表明，阿维鲁单抗提供了长期疗效益处，从维持治疗开始测量的中位OS为23.8个月，从1L化疗开始29.7个月。在亚组中观察到更长的OS，包括接受1L顺铂+吉西他滨的患者，接受4或6个周期1L化疗的患者，有完全反应的患者，部分响应,或稳定的疾病作为1L诱导化疗的最佳反应。在接受≥1年avelumab治疗的患者中未发现新的安全性信号。接受顺铂或卡铂联合吉西他滨治疗的患者的毒性相似。其他临床数据集，包括在欧洲进行的非干预研究，美国,亚洲,已证实阿维鲁单抗1L维持的疗效。阿维鲁单抗维持治疗后的潜在后续治疗选择包括抗体-药物偶联物（enfortumabvedotin或sacituzumabgovitecan），erdafitinib在生物标志物选择的患者中，在合适的患者中进行铂类再激发，非铂类化疗,和临床试验参与；然而，需要确定最佳治疗顺序的证据。正在进行的基于avelumab的联合方案作为维持治疗的试验有可能发展晚期UC患者的治疗前景。
