OBJECTIVES : KEYNOTE-426 demonstrated statistically and clinically meaningful improvements in overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) in ccmRCC subjects treated with P+A versus (vs) sunitinib. This NMA synthesized RCT evidence to indirectly compare the relative treatment effects of P+A vs other therapies. METHODS : A systematic literature review identified RCTs of approved or investigational 1L treatments of mRCC. Fixed-effect Bayesian NMA was conducted to determine the relative efficacy of treatments; OS, PFS [hazard ratios (HRs)] and ORR (odds ratio [OR]) were presented with 95% credible intervals (CrIs). RESULTS : 18 RCTs (total ITT population: 10,547) that evaluated 17 interventions were identified (10 evaluable for OS, 14 for PFS, 13 for ORR). P+A showed statistically significant OS benefit over 7 out of 9 interventions evaluated [ranging from interferon-alpha (IFN-α) (HR=0.43, 0.29-0.64) through bevacizumab (B) + IFN-α, B + temsirolimus (B+T), sunitinib, placebo, pazopanib to atezolizumab + bevacizumab (A+B) [HR=0.65, 0.43-0.99]. OS benefit favored P+A vs avelumab + axitinib (A+A) [HR=0.68, 0.43-1.09] and vs nivolumab + ipilimumab (N+I) [HR=0.75, 0.51-1.09], but was not statistically significant. P+A showed statistically significant PFS benefit over 11 out of 13 interventions evaluated [ranging from placebo (HR=0.26, 0.16-0.42) through sorafenib, IFN-α, axitinib, tivozanib, B+T, B+ IFN-α, pazopanib, atezolizumab, sunitinib to A+B (HR=0.77, 0.60-0.99)]; PFS benefit favored P+A over N+I [HR=0.81, 0.64-1.03] but was not statistically significant, and P+A showed no difference compared to A+A [HR=1.00, 0.76-1.32]. P+A showed statistically significant ORR benefit over 11 out of 12 interventions evaluated [ranging from placebo (OR=25.22, 7.93-110.97) , sorafenib, IFN-α, axitinib, B+T, B+ IFN-α, atezolizumab, A+B, sunitinib, pazopanib to N+I (OR=1.95, 1.35-2.82)]; results favored A+A over P+A [OR=0.86, 0.58-1.27], but were not statistically significant. CONCLUSIONS : These analyses suggest that P+A provides significant OS, PFS and ORR benefits when indirectly compared to majority of 1L ccmRCC treatments.