铂类化疗（ChT）已成为转移性尿路上皮癌（mUC）的标准一线治疗方法。本研究的目的是评估诱导 avelumab、随后 avelumab 联合卡铂-吉西他滨 (carbo/gem)、随后 avelumab 维持治疗的使用情况。我们测试了诱导免疫疗法 (IO) 可以增强对 ChT 的反应并防止其对免疫细胞产生有害影响的假设。INDUCOMAIN 是一项由研究者发起的多中心、随机、开放标签 II 期研究，评估诱导 avelumab 的安全性和有效性与卡铂/gem（B 组）相比，先使用卡铂-吉西他滨-avelumab，然后进行 avelumab 维持治疗（A 组）。资格标准包括 mUC 患者、既往未接受全身治疗以及根据 Galsky 标准不适合使用顺铂。根据是否存在内脏转移和东部肿瘤合作组表现状态 0-1 与 2 对患者进行分层。主要终点是客观缓解率 (ORR)。次要终点包括无进展生存期 (PFS)、总生存期 (OS) 和安全性。纳入了 85 名患者，并分别随机分配到 A 组 (n = 42) 和 B 组 (n = 43)。治疗组之间的 ORR 相似：A 组为 59.5%，B 组为 53.5%（P = 0.57）。 A 组中有 14 名患者 (33%) 在首次反应评估之前或首次反应评估时早期进展/死亡，而 B 组有 3 名患者 (7%)。A 组的中位 OS 为 11.1 个月，B 组为 13.2 个月 [风险比 ( HR) 0.91，95% 置信区间 (CI) 0.57-1.46，P = 0.69]。 A 组的中位 PFS 为 6.9 个月，而 B 组为 7.4 个月（HR 0.99，95% CI 0.61-1.60，P = 0.95）。 A 组中 70.7% 的患者和 B 组中 72.1% 的患者发生了 3-4 级的治疗相关不良事件。未发现程序性死亡配体 1 表达的预测作用。诱导 avelumab 可以增强疗效的假设随后的 ChT 未得到证实。在 ChT 之前单独进行 IO 作为诱导并不是一个充分的策略。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Platinum-based chemotherapy (ChT) has been the standard first-line treatment for metastatic urothelial carcinoma (mUC). The purpose of this study was to evaluate the use of induction avelumab followed by avelumab in combination with carboplatin-gemcitabine (carbo/gem) followed by avelumab maintenance. We tested the hypothesis that induction immunotherapy (IO) could enhance the response to ChT and prevent its detrimental effect on immune cells.INDUCOMAIN is a multicenter, randomized, investigator-initiated, open-label phase II study evaluating the safety and efficacy of induction avelumab before carboplatin-gemcitabine-avelumab, followed by avelumab maintenance (arm A), compared to carbo/gem (arm B). Eligibility criteria included patients with mUC, no prior systemic therapy, and ineligibility for cisplatin by Galsky criteria. Patients were stratified by the presence/absence of visceral metastasis and Eastern Cooperative Oncology Group performance status 0-1 versus 2. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.Eighty-five patients were included and randomized to arm A (n = 42) and arm B (n = 43), respectively. ORR was similar between treatment arms: 59.5% in arm A and 53.5% in arm B (P = 0.57). Fourteen patients (33%) in arm A early progressed/died before or at first response assessment, compared to three patients (7%) in arm B. Median OS was 11.1 months in arm A and 13.2 months in arm B [hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.57-1.46, P = 0.69]. Median PFS was 6.9 months in arm A versus 7.4 months in arm B (HR 0.99, 95% CI 0.61-1.60, P = 0.95). Treatment-related adverse events of grade 3-4 occurred in 70.7% of patients in arm A and in 72.1% in arm B. No predictive role of programmed death-ligand 1 expression was found.The hypothesis that induction avelumab could enhance the efficacy of subsequent ChT was not proven. Administering IO alone as induction before ChT is not an adequate strategy.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.