PCN23 UPDATED NETWORK META-ANALYSIS OF TREATMENTS IN FIRST-LINE ADVANCED/METASTATIC INTERMEDIATE- OR POOR-RISK RENAL CELL CARCINOMA

New data from CheckMate-214 (CM-214; NCT02231749) with a minimum follow-up of 30 months, comparing nivolumab+ipilimumab to sunitinib for first-line advanced/metastatic intermediate- or poor-risk renal cell carcinoma (1L RCC), has become available. The objective of this study was to update a previously conducted network meta-analysis (NMA) with more mature survival data from CM-214. The NMA by Laliman et al. (2018) was updated with the overall survival (OS) and progression-free survival (PFS) per investigator hazard ratios (HR) from CM-214. Efficacy data of comparators were based on the previously conducted systematic literature review (SLR). Fixed- and random-effects Bayesian NMAs were fitted on HRs of OS and PFS. Eight studies were included in the OS network comparing eight therapies, thirteen studies formed a network comparing fourteen therapies for PFS. Nivolumab+ipilimumab was found to significantly improve OS compared to five comparators: sunitinib (HR:0.66 95%CrI[0.54,0.80]), interferon (HR:0.50 95%CrI[0.35,0.71]), bevacizumab+interferon (HR:0.59 95%CrI[0.39,0.85]), temsirolimus (HR:0.69 95%CrI[0.46,0.99]) and temsirolimus+interferon (HR:0.53 95%CrI[0.34,0.77]). The other comparisons included nivolumab+ipilimumab versus cabozantinib (HR:0.85 95%CrI[0.52,1.31]) and pazopanib (HR:0.76 95%CrI[0.56,1.01]). Nivolumab+ipilimumab significantly improved PFS compared to seven comparators: sunitinib (HR:0.77 95%CrI[0.65,0.91]), interferon (HR:0.32 95%CrI[0.19,0.51]), bevacizumab+interferon (HR:0.55 95%CrI[0.29,0.95]), everolimus (HR:0.51 95%CrI[0.33,0.76]), temsirolimus (HR:0.48 95%CrI[0.27,0.80]), temsirolimus+interferon (HR:0.44 95%CrI[0.25,0.73]) and placebo (HR:0.36 95%CrI[0.15,0.76]). The other comparisons included nivolumab+ipilimumab versus bevacizumab+temsirolimus (HR:0.53 95%CrI[0.25,1.01]), pazopanib (HR:0.71 95%CrI[0.33,1.39]), sorafenib (HR:0.78 95%CrI[0.30,1.73]), axitinib (HR:0.96 95%CrI[0.32,2.28]), tivozanib (HR:0.97 95%CrI[0.32,2.38]) and cabozantinib (HR:1.65 95%CrI[1.01,2.55]). For both OS and PFS, results were presented according to the fixed-effects model, as the random effects model did not converge. Nivolumab+ipilimumab was statistically superior to most comparators tested for OS and PFS, representing a significant advance for 1L RCC patients. This result is in line with the previous NMA, showing robustness of the efficacy estimates and benefit of nivolumab+ipilimumab as 1L treatment for RCC.