The median PFS was 15.1 months (95% CI, 12.6 to 17.7) in the pembrolizumab plus axitinib group and 11.1 months (95% CI, 8.7 to 12.5) in the sunitinib group. In exploratory analysis, this benefit was seen across all subgroups including PD-L1 negative tumors. The hazard ratio for death in the pembrolizumab plus axitinib group was 0.53 (95% CI 0.38-0.74 p < 0.0001). The median overall survival was not reached in either group, however the estimated percent alive at 1 year was 89.9% (95% CI, 86.4 to 92.4) in the pembrolizumab–axitinib group and 78.3% (95% CI, 73.8 to 82.1) in the sunitinib group. Roughly 60% of patients had PD-L1 positive tumors. There were no major differences in baseline characteristics between the two groups. In the Keynote 426 trial, 432 patients were assigned to the pembrolizumab plus axitinib arm and 429 were assigned to the sunitinib arm. Patients were stratified according to IMDC risk score (a composite score of functional status and laboratory values), region, and PD-L1 status. A key secondary endpoint in both trials was objective response rate (ORR) as defined by RECIST v1.1. In the JAVELIN trial, the primary endpoints were OS and PFS in the PD-L1 positive cohort, OS and PFS in the overall population were secondary endpoints. The primary endpoints in the Keynote 426 trial were progression free survival (PFS) as defined by RECIST v1.1 and overall survival (OS) in the entire enrolled population. Central nervous system involvement was a key exclusion criterion. Both trials enrolled newly diagnosed metastatic RCC patients over 18 years old with a functional status of ECOG 0-1. In Keynote 426, the PD-L1 inhibitor pembrolizumab plus axitinib (a TKI) are compared to sunitinib whereas in the JAVELIN trial, the PD-1 inhibitor avelumab plus axitinib are compared to sunitinib. In the two phase III randomized control trials discussed here, Keynote 426 2 and JAVELIN 101, 3 the investigators pursue the question of combined TKI and ICI as first line therapy in RCC. 1 Preclinical data suggests that TKIs could be synergistic with ICI. The past decade has seen an explosion of available therapies in renal cell carcinoma (RCC), beginning with the adoption of sunitinib and the other tyrosine kinase inhibitors (TKIs), followed more recently by the adoption of immune checkpoint inhibitors (ICI) as first and second line therapy. Review of Keynote 426 and JAVELIN Renal 101 clinical trials (Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma and Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma)Är.
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