Patients with EGFR-mutant NSCLC treated with EGFR-TKIs who had tumor genomic profiling were included. Alterations in TP53 and five additional TSGs (RB1, NF1, ARID1A, BRCA1 and PTEN) were used to stratify the cohort into three subgroups: patients with tumors harboring a TP53 mutation plus a mutation in ≥1 additional TSG (TP53mut/TSGmut), a TP53 mutation without additional TSG mutations (TP53mut/TSGwt), and TP53wt....Inferior outcomes in TP53mut/TSGmut tumors were also seen in patients receiving osimertinib as second-line therapy.