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.
Published Version
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