直到最近，晚期尿路上皮癌 (UC) 的标准一线治疗还是以铂类为基础的联合化疗，然后对无进展性疾病 (PD) 的患者进行 avelumab 维持治疗。对于经历 PD 或复发的晚期 UC 患者，标准护理治疗是基于 3 期 KEYNOTE-045 研究的派姆单抗单一疗法。 KEYNOTE-045 研究的事后分析通过对先前铂类化疗的最佳反应评估了派姆单抗与化疗相比的疗效。一线铂类化疗后进展或复发的晚期 UC 患者被随机分配为 1 组： 1 接受派姆单抗 200 mg 每 3 周 (Q3W) 治疗 ≤2 年，或接受研究者选择的化疗（紫杉醇 [175 mg/m2]、多西他赛 [75 mg/m2] 或长春氟宁 [320 mg/m2]，每个 Q3W ）。终点包括从死亡前最后一次治疗开始的总生存期 (OS)、客观缓解率 (ORR) 以及根据实体瘤 1.1 版缓解评估标准从首次缓解之日起的缓解持续时间 (DOR)。根据先前对一线铂类化疗的反应，在所有组中观察到对派姆单抗的客观反应。各个亚组中，派姆单抗组的中位 OS、ORR 和中位 DOR 在数值上均高于化疗组。对既往铂类化疗反应最佳的 PD 患者的 OS 结果最差。局限性包括缺乏正式的假设检验。与化疗相比，观察到二线派姆单抗的延长 OS 和持久反应，与先前铂类化疗的反应或类型无关。这些发现进一步支持派姆单抗作为晚期 UC 的二线治疗。版权所有 © 2024 Merck Sharp

Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy.Patients with advanced UC that progressed or recurred after first-line platinum-based chemotherapy were randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 wk (Q3W) for ≤2 yr or investigator's choice of chemotherapy (paclitaxel [175 mg/m2], docetaxel [75 mg/m2], or vinflunine [320 mg/m2], each Q3W). Endpoints included overall survival (OS) from the initiation of the last treatment prior to death, objective response rate (ORR), and duration of response (DOR) as per Response Evaluation Criteria in Solid Tumors version 1.1 from the date of the first response.An objective response to pembrolizumab was observed in all groups in terms of a prior response to first-line platinum-based chemotherapy. Median OS, ORR, and median DOR were numerically greater with pembrolizumab than with chemotherapy across subgroups. Patients with PD as the best response to prior platinum-based chemotherapy had the poorest OS outcomes. Limitations include a lack of formal hypothesis testing.When compared with chemotherapy, prolonged OS and durable responses to second-line pembrolizumab were observed independently of the response to or type of prior platinum-based chemotherapy. These findings further support pembrolizumab as second-line treatment for advanced UC.Copyright © 2024 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier B.V. All rights reserved.