This cohort study examined 104 patients with unresectable locally advanced NSCLC....Patients were grouped according to the presence of non–KRAS driver variations (EGFR exon 19 deletion, EGFR exon 20 insertion, EGFR exon 21 mutation [L858R], ERBB2 exon 20 insertion, EML4-ALK fusion, MET exon 14 skipping, NTRK2 fusion), KRAS driver variations, or no driver variations....Patients with driver variations, both non–KRAS (8.4 months) and KRAS (8.0 months), had significantly shorter median PFS times (8.4 months vs 40.1 months; HR, 2.75; 95% CI, 1.64-4.62; P < .001) (Figure 1). On multivariate analysis, non–KRAS driver variation, KRAS driver variation, stage IIIC disease, and ECOG 2 were associated with worse PFS (Table 2)....In this cohort study, driver variations in patients with unresectable locally advanced NSCLC were associated with significantly shorter PFS time after definitive chemoradiation and consolidative durvalumab.