BACKGROUND Patients with metastatic urothelial carcinoma (mUC) who progress after platinum-based chemotherapy have had few treatment options and uniformly poor outcomes. Atezolizumab (anti-programmed death-ligand 1) was approved in the USA for cisplatin-ineligible and platinum-treated mUC based on IMvigor210, a phase 2, single-arm, two-cohort study. OBJECTIVE To evaluate the efficacy and safety of atezolizumab by the number of prior lines of systemic therapy in patients with pretreated mUC. DESIGN, SETTING, AND PARTICIPANTS IMvigor210 enrolled 315 patients with mUC with progression during or following platinum-based therapy at 70 international sites between May 2014 and November 2014. Key inclusion criteria included age ≥18 yr, creatinine clearance ≥30ml/min, and Eastern Cooperative Oncology Group performance status 0-1, with no limit on prior lines of treatment. INTERVENTION Patients in this cohort received atezolizumab 1200mg intravenously every 3 wk until loss of clinical benefit. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Centrally assessed Response Evaluation Criteria In Solid Tumors v1.1 objective response rate (ORR), median duration of response, overall survival (OS), and adverse events were evaluated by prior treatment. Potential differences between subgroups were evaluated using log-rank (for OS) and chi-square (for ORR and adverse events frequencies) testing. RESULTS AND LIMITATIONS Three hundred and ten patients were efficacy and safety evaluable (median follow-up, 21 mo). Objective responses and prolonged OS occurred across all prespecified subgroups; median duration of response was not reached in most subgroups. In patients without prior systemic mUC therapy (first-line subgroup), ORR was 25% (95% confidence interval: 14-38), and median OS was 9.6 mo (95% confidence interval: 5.9-15.8). No significant differences in efficacy or toxicity by therapy line were observed. CONCLUSIONS Atezolizumab demonstrated comparable efficacy and safety in previously treated patients with mUC across all lines of therapy evaluated. PATIENT SUMMARY We investigated effects of previous treatment in patients with metastatic urothelial carcinoma that progressed after platinum-based therapy. Atezolizumab was active and tolerable no matter how many treatment regimens patients had received. ClinicalTrials.gov, NCT02108652.

中文翻译：

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Atezolizumab 治疗铂金治疗的局部晚期或转移性尿路上皮癌：先前治疗方案数量的结果。

背景 铂类化疗后进展的转移性尿路上皮癌 (mUC) 患者几乎没有治疗选择，且预后均不佳。Atezolizumab（抗程序性死亡配体 1）基于 IMvigor210（一项 2 期、单臂、双队列研究）在美国被批准用于不符合顺铂条件且接受铂治疗的 mUC。目的通过在接受过治疗的 mUC 患者中通过先前系统治疗线的数量来评估 atezolizumab 的疗效和安全性。设计、设置和参与者 IMvigor210 在 2014 年 5 月至 2014 年 11 月期间在 70 个国际研究中心招募了 315 名在铂类治疗期间或之后出现进展的 mUC 患者。关键纳入标准包括年龄≥18 岁、肌酐清除率≥30ml/min 和东部合作肿瘤学组表现状态 0-1，对先前的治疗线没有限制。干预 该队列中的患者每 3 周静脉注射 1200mg atezolizumab，直至失去临床获益。结果测量和统计分析 集中评估的反应评价标准 在实体瘤 v1.1 中，客观反应率 (ORR)、中位反应持续时间、总生存期 (OS) 和不良事件通过先前治疗进行评价。使用对数秩（对于 OS）和卡方（对于 ORR 和不良事件频率）检验评估亚组之间的潜在差异。结果和局限性 310 名患者可评估疗效和安全性（中位随访时间为 21 个月）。所有预先指定的亚组均出现客观反应和延长 OS；大多数亚组未达到中位缓解持续时间。在未接受过全身 mUC 治疗的患者（一线亚组）中，ORR 为 25%（95% 置信区间：14-38），中位 OS 为 9.6 个月（95% 置信区间：5.9-15.8）。没有观察到不同治疗线的疗效或毒性有显着差异。结论 Atezolizumab 在所有评估过的治疗线中对先前治疗过的 mUC 患者表现出相当的疗效和安全性。患者总结 我们调查了先前治疗对铂类治疗后进展的转移性尿路上皮癌患者的影响。无论患者接受了多少治疗方案，Atezolizumab 都是有效且可耐受的。ClinicalTrials.gov，NCT02108652。没有观察到不同治疗线的疗效或毒性有显着差异。结论 Atezolizumab 在所有评估过的治疗线中对先前治疗过的 mUC 患者表现出相当的疗效和安全性。患者总结 我们调查了先前治疗对铂类治疗后进展的转移性尿路上皮癌患者的影响。无论患者接受了多少治疗方案，Atezolizumab 都是有效且可耐受的。ClinicalTrials.gov，NCT02108652。没有观察到不同治疗线的疗效或毒性有显着差异。结论 Atezolizumab 在所有评估过的治疗线中对先前治疗过的 mUC 患者表现出相当的疗效和安全性。患者总结 我们调查了先前治疗对铂类治疗后进展的转移性尿路上皮癌患者的影响。无论患者接受了多少治疗方案，Atezolizumab 都是有效且可耐受的。ClinicalTrials.gov，NCT02108652。患者总结 我们调查了先前治疗对铂类治疗后进展的转移性尿路上皮癌患者的影响。无论患者接受了多少治疗方案，Atezolizumab 都是有效且可耐受的。ClinicalTrials.gov，NCT02108652。患者总结 我们调查了先前治疗对铂类治疗后进展的转移性尿路上皮癌患者的影响。无论患者接受了多少治疗方案，Atezolizumab 都是有效且可耐受的。ClinicalTrials.gov，NCT02108652。