Boyer M, Şendur MAN, Rodríguez-Abreu D, et al. - In patients suffering from metastatic non–small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations, researchers performed this randomized, double-blind, phase 3 KEYNOTE-598 trial to determine if the addition of ipilimumab to pembrolizumab would result in improved effectiveness vs pembrolizumab alone. All eligible patients (n = 568) were administered pembrolizumab 200 mg every 3 weeks for up to 35 doses, and then randomized 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses (n = 284 in each group). For pembrolizumab-ipilimumab vs pembrolizumab-placebo, the estimated median overall survival was 21.4 months vs 21.9 months, respectively, and the estimated median progression-free survival was 8.2 months vs 8.4 months, respectively. Therefore, no improved efficacy was conferred by ipilimumab added to pembrolizumab and this treatment strategy was found to be related to greater toxicity when compared with pembrolizumab alone as first-line therapeutic choice for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. The use of pembrolizumab-ipilimumab instead of pembrolizumab monotherapy in this population is not supported by these findings.