Background: Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (P þ A), and nivolumab plus ipilimumab (N þ I) as first-line treatments, from the Brazilian private perspective. Methods: Overall survival (OS) and progression-free survival (PFS) data for intermediate-and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for P þ A and N þ I, respectively, versus sunitinib as mRCC first-line treatment. Results: Considering a 12-month time horizon, 6 patients should be treated with P þ A to prevent one death with sunitinib use, resulting in a COPE of 3,773,865 BRL. Using N þ I, NNT for 12-month OS rate was 13 compared to sunitinib, with a COPE of 6,357,965 BRL. Regarding PFS data, NNT was also 6 when comparing P þ A versus sunitinib, with an estimated COPE of 3,773,865 BRL. Estimated NNT was 20 comparing N þ I and sunitinib, resulting in a COPE of 10,172,744 BRL. Cost differences between two treatment options, reached more than 6 million BRL for PFS, and 2 million BRL for OS. Conclusion: At the 12-month landmark, P þ A suggests better economic scenario versus N þ I as firstline mRCC treatment option for intermediate-and poor-risk groups, through an indirect comparison using sunitinib as a common comparator.