Currently, a substantial number of trials have reported excellent outcomes of these combination modalities in several cancer types [21–30], which facilitated FDA approval of the nivolumab plus ipilimumab combination as first-line treatment for BRAF V600 wild-type unresectable or metastatic melanoma [42] and pembrolizumab plus pemetrexed and carboplatin as first-line treatment for metastatic NSCLC, irrespective of PD-L1 expression [28]. This evidence concerns the gene BRAF and metastatic melanoma.