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Antiangiogenic therapy combined with immune checkpoint blockade in urothelial cancer: Systematic review and
Mohammad Jad Moussa1, Iuliia Kovalenko2, Emanuele Crupi3,4
1Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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.
Insights
Combining immune checkpoint inhibitors (ICI) with antiangiogenic agents shows a 27% objective response rate in urothelial cancer (UC). Efficacy is lower in patients previously treated with ICI, highlighting the need for better patient selection in refractory settings.
Area of Science:
- Oncology
- Urothelial Carcinoma Research
- Cancer Therapeutics
Background:
- Antiangiogenic therapy has been explored for urothelial cancer (UC) but has not yet reached clinical application.
- Immune checkpoint inhibitors (ICI) represent a significant advancement in cancer treatment.
Purpose of the Study:
- To systematically review and meta-analyze clinical trials evaluating the efficacy of combining ICI with antiangiogenic agents in UC patients.
- To assess the impact of prior ICI exposure on treatment outcomes.
Main Methods:
- A systematic literature search was conducted following PRISMA guidelines to identify relevant trials.
- Nine studies with 14 cohorts (621 patients) were included, analyzing data using a frequentist meta-analysis approach.
- Patients were categorized into ICI-naïve (ICI-N) and ICI-exposed (ICI-E) groups.
Main Results:
- The overall objective response rate (ORR) for ICI plus antiangiogenics in UC was 27%.
- ICI-naïve patients demonstrated a higher ORR (34%) compared to ICI-exposed patients (16%).
- Median overall survival and progression-free survival varied between the ICI-N and ICI-E groups.
Conclusions:
- The combination of ICI and antiangiogenics yields a lower ORR in urothelial cancer patients with prior ICI exposure.
- Significant variability in outcomes suggests potential influence from different antiangiogenic agents or trial design.
- Future research should focus on improved patient selection strategies for this combination therapy, particularly in ICI-refractory cases.
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