Antiangiogenic Therapy Combined With Immune Checkpoint Blockade in Urothelial Cancer: Systematic Review and Meta-Analysis

Authors

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

Publication Date

12-1-2024

Journal

Bladder Cancer

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.

Keywords

antiangiogenic therapy, bladder cancer, clinical outcomes, combination therapy, immune checkpoint inhibitors, immunotherapy, metastatic urothelial cancer, tyrosine kinase inhibitors, urothelial cancer.

DOI

10.1177/23523735241296763

PMID

40035076

PMCID

PMC11864237

PubMedCentral® Posted Date

12-20-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes