OBJECTIVES: To investigate the relative efficacy of nivolumab, a new humanized IgG4 monoclonal antibody, in combination with ipilimumab against other therapies in previously untreated (1L) advanced or metastatic renal-cell carcinoma (RCC) patients with intermediate or poor prognosis.

METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials (RCT) in the population of interest. The feasibility of a NMA was assessed by comparing variability in trial design, population baseline characteristics and outcomes definition. Both fixed- and random-effects Bayesian NMAs were fitted on hazard ratios (HR) of Overall Survival (OS) and Progression-Free Survival (PFS).

RESULTS: In total, seventy-two RCTs were identified among which thirteen reported HRs for OS or PFS in the population of interest. No meaningful differences were found in the baseline characteristics and inclusion/exclusion criteria. Eight studies were included in the OS network comparing eight therapies. Nivolumab+ipilimumab was found to have the highest probability of being the best treatment (84%) and significantly improved OS compared to six comparators: sunitinib (HR:0.63 95%CrI[0.50,0.79]), interferon (HR:0.47 95%CrI[0.33,0.69]), pazopanib (HR:0.72 95%CrI[0.52,0.99]), bevacizumab with interferon (HR:0.55 95%CrI[0.37,0.83]), temsirolimus (HR:0.64 95%CrI[0.43,0.96]) and temsirolimus with interferon (HR:0.49 95%CrI[0.32,0.75]). For PFS, the thirteen included studies formed a network comparing fourteen therapies. Nivolumab+ipilimumab significantly improved PFS, compared to sunitinib (HR:0.82 95%CrI[0.68,0.99]), interferon (HR:0.33 95%CrI[0.20,0.54]), bevacizumab with interferon (HR:0.31 95%CrI[0.31,0.99]), everolimus (HR:0.53 95%CrI[0.35,0.81]), temsirolimus (HR:0.49 95%CrI[0.29,0.82]), temsirolimus with interferon (HR:0.44 95%CrI[0.26,0.75]) and placebo (HR:0.34 95%CrI[0.15,0.78]). For both OS and PFS, results were presented according to the fixed-effects model, which was selected based on deviance information criteria (DIC).

CONCLUSIONS: Nivolumab+ipilimumab was statistically superior to almost all comparators tested for OS and PFS and therefore represents a significant advance for patients in 1L RCC.