Background:

Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy.

Methods:

Data were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses.

Results:

The study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p < 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p < 0.001), and 2 months for patients who did not receive further active treatment (p < 0.001).

Conclusions:

Chemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line.

中文翻译：

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转移性尿路上皮癌患者进展为免疫检查点抑制剂后的临床结果：Meet-Uro 组的回顾性分析（Meet-URO 1 研究）

背景：

免疫检查点抑制剂 (ICI) 目前是先前含铂化疗失败后转移性尿路上皮癌 (mUC) 的标准治疗方法。ICI 进展后进一步治疗的选择是一个新的挑战，并且缺乏数据支持。我们旨在检查 mUC 患者在进展为 ICI 后的结果，尤其是在接受化疗时。

方法：

数据是从 14 个意大利中心的疾病进展为抗程序性死亡 1 (PD-1) 或程序性死亡配体 1 (PD-L1) 治疗的 mUC 患者的临床记录中回顾性收集的。根据 ICI 治疗设置将患者分为 SALVAGE（即 ICI 在铂类化疗后提供⩾二线治疗）和 NAÏVE（即一线治疗）组。使用 Kaplan-Meier 方法计算无进展生存期 (PFS) 和总生存期 (OS) 率，并在亚组之间进行比较。Cox 回归评估了进展为 ICI 后治疗对 OS 的影响。客观反应率 (ORR) 计算为部分和完全放射学反应的总和。

结果：

研究人群包括 201 名在 ICI 后进展的 mUC 患者：59 名在 NAÏVE 队列中，142 名在 SALVAGE 队列中。总体而言，52 名患者在 ICI 进展后接受了化疗（25.9%），20 名（9.9%）在进展后接受了 ICI，115 名（57.2%）只接受了最佳支持治疗，14 名（7.0%）接受了研究药物。ICI 后化疗的客观反应率为 23.1%（NAÏVE 组为 28.0%，SALVAGE 组为 18.5%）。对于 NAÏVE 组，ICI-PD 后化疗的中位 PFS 和 OS 分别为 5 个月（95% 置信区间 [CI]：3-11）和 13 个月（95% CI：7-NA）；SALVAGE 组分别为 3 个月（95% CI：2-NA）和 9 个月（95% CI：6-NA）。接受化疗的患者从 ICI 开始的总生存期为 17 个月（风险比 [HR] = 0.09，p< 0.001)，而在进展后接受 ICI 的患者为 8 个月（HR = 0.13，p < 0.001），未接受进一步积极治疗的患者为 2 个月（p < 0.001）。

结论：

对于 mUC 患者，ICI 进展后进行化疗是可取的，无论治疗线如何。