Combining Immune Checkpoint and VEGFR Inhibition in Favorable Risk and Elderly Patients With Metastatic Renal Cell Carcinoma

Abstract

Background: Immune checkpoint inhibitors and vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors are the most commonly used medications in metastatic renal cell carcinoma (mRCC). Recently, large clinical trials have shown favorable outcomes in patients treated with combined immune checkpoint plus VEGFR inhibition compared with VEGFR inhibition alone. However, the benefit among favorable risk (based on International Metastatic Renal Cell Carcinoma Database Consortium score) and elderly (age > 65 years) patients was not clear, leading to a discrepancy between United States Food and Drug Administration and European Association of Urology recommendations.

Materials and methods: We searched available literature for phase III randomized clinical trials evaluating the efficacy of combining immunotherapy plus VEGF/VEGFR inhibitors versus standard of care in patients with previously untreated mRCC. Combinations that were included in United States Food and Drug Administration recommendations or European Association of Urology guidelines were used for analysis. We performed a meta-analysis with a random effects model to evaluate the efficacy of immunotherapy-VEGFR inhibitor combinations compared with sunitinib in favorable risk and elderly patients.

Results: Our analysis demonstrated that progression-free survival (PFS) was significantly prolonged with combination therapy compared with sunitinib in patients with age > 65 years (hazard ratio, 0.66; 95% confidence interval, 0.52-0.84; P = .001). The PFS in favorable risk disease was improved with combination therapy compared with sunitinib, but the difference was not statistically significant (hazard ratio, 0.68; 95% confidence interval, 0.46-1.01; P = .055).

Conclusion: Our meta-analysis strengthens the trend of beneficial effect in prolonging PFS in both subgroups compared with each trial alone, indicating that favorable risk and elderly patients with mRCC likely benefit from combining programmed cell death 1 or programmed cell death-ligand 1 and VEGFR inhibition.

Keywords: Avelumab; Axitinib; Favorable risk; Immune checkpoint inhibitors; Pembrolizumab.