Efficacy and prognostic analysis of chemo-immunotherapy after TKI resistance in EGFR-mutant non-small cell lung cancer with TP53 or KRAS co-mutations

In the first-line setting, patients with an EGFR single mutation treated with EGFR-TKIs had a longer median PFS than those with EGFR/TP53 and EGFR/KRAS co-mutations (14.1 vs 10.4 and 10.9 months, respectively; both <i>P</i> < 0.0001), whereas no statistically significant difference was observed between the two co-mutation subgroups (<i>P</i> = 0.174). Following the development of resistance, all patients received platinum-based doublet chemotherapy plus immunotherapy; in the second-line setting, median PFS was modestly longer in the co-mutation groups compared with the single-mutation group (EGFR/TP53: 5.2 months; EGFR/KRAS: 5.0 months; EGFR single mutation: 3.9 months; overall log-rank <i>P</i> < 0.0001), with no significant difference between the TP53 and KRAS subgroups (<i>P</i> = 0.174). These associations were evident on Kaplan-Meier curves (with numbers at risk) and log-rank testing, and were supported by multivariable Cox models adjusted for age, sex, smoking history, clinical stage, histology, and ECOG performance status.