Antiangiogenic therapy combined with immune checkpoint blockade in urothelial cancer: Systematic review and meta-analysis.

IF 1 4区医学 Q4 ONCOLOGY Bladder Cancer Pub Date : 2024-12-20 eCollection Date: 2024-12-01 DOI:10.1177/23523735241296763

Mohammad Jad Moussa, Iuliia Kovalenko, Emanuele Crupi, Ekaterina Proskuriakova, Yimin Geng, Giuseppe Fallara, Raed Benkhadra, Daniele Raggi, Matthew T Campbell, Pavlos Msaouel, Omar Alhalabi

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Abstract

Background: Antiangiogenic therapy had been tested in urothelial cancer (UC) without reaching the clinic.

Objective: We provide a systematic review and meta-analysis of trials to assess efficacy of immune checkpoint inhibitors (ICI) combined with antiangiogenic agents in UC.

Methods: Following PRISMA guidelines, we searched for trials with at least one arm of patients with UC treated with ICI plus antiangiogenics. Data were analyzed with the "meta" package from R using a one-staged frequentist meta-analysis.

Results: After screening 13,708 titles and abstracts, 9 studies were selected for analysis with 14 identified cohorts comprising 621 patients: 448 were ICI-naïve (ICI-N) and 173 were ICI-exposed (ICI-E). The estimated objective response rate (ORR) in all patients was 27% (21-35). In the ICI-N group, ORR was 34% (28-41). Conversely, the ICI-E group had a lower ORR of 16% (9-28). This difference was mainly driven by a higher partial response rate of 27% (23-31) in ICI-N group compared to 13% (8-20) in the ICI-E group. Disease control rate was 72% (66-77) ICI-N group vs. 71% (64-78) in ICI-E group. Median overall survival ranged from 6.4 to 24.9 months in the ICI-N group, and 8.2 to 10.4 months in ICI-E group. Median progression free survival ranged from 1.9 to 10.1 months and from 3 to 3.9 months in both groups, respectively.

Conclusion: ORR with ICI plus antiangiogenics was lower after prior ICI exposure, with substantial variability estimates among included trials, either due to differences among antiangiogenic agents used or trial-related factors. Future exploration of ICI combined with antiangiogenics in UC, especially in ICI-refractory setting, will benefit from better patient selection.

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背景：抗血管生成疗法已在尿道癌（UC）中进行了试验，但尚未进入临床：我们对免疫检查点抑制剂（ICI）联合抗血管生成药物治疗尿道癌的疗效评估试验进行了系统回顾和荟萃分析：根据PRISMA指南，我们搜索了至少有一个UC患者接受ICI联合抗血管生成药物治疗的试验。我们使用R软件包 "meta "对数据进行了单阶段频数主义荟萃分析：在筛选了13708篇标题和摘要后，选出了9项研究进行分析，共确定了14个队列，包括621名患者：其中 448 例为 ICI 未接受者（ICI-N），173 例为 ICI 暴露者（ICI-E）。所有患者的估计客观反应率（ORR）为 27% (21-35)。在 ICI-N 组中，ORR 为 34% (28-41)。相反，ICI-E 组的客观反应率较低，为 16% (9-28)。造成这一差异的主要原因是，ICI-N组的部分反应率为27%（23-31），高于ICI-E组的13%（8-20）。ICI-N组的疾病控制率为72%（66-77），而ICI-E组为71%（64-78）。ICI-N 组的中位总生存期为 6.4 至 24.9 个月，ICI-E 组为 8.2 至 10.4 个月。两组的中位无进展生存期分别为1.9至10.1个月和3至3.9个月：结论：ICI联合抗血管生成药物的ORR在既往接触过ICI后较低，所纳入试验的估计值存在很大差异，这可能是由于所使用的抗血管生成药物不同或试验相关因素所致。未来对 ICI 联合抗血管生成药物治疗 UC 的探索，尤其是在 ICI 难治性病例中，将受益于更好的患者选择。

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来源期刊

Bladder Cancer Medicine-Urology

CiteScore

1.60

自引率

0.00%

发文量

期刊介绍： Bladder Cancer is an international multidisciplinary journal to facilitate progress in understanding the epidemiology/etiology, genetics, molecular correlates, pathogenesis, pharmacology, ethics, patient advocacy and survivorship, diagnosis and treatment of tumors of the bladder and upper urinary tract. The journal publishes research reports, reviews, short communications, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that expedites our fundamental understanding and improves treatment of tumors of the bladder and upper urinary tract.