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

Objective: To investigate the impact of co-mutations of EGFR with TP53 or KRAS on the prognosis of non-small cell lung cancer (NSCLC) patients, and the efficacy of platinum-based doublet chemotherapy plus immunotherapy after EGFR-TKI resistance. Methods: This was a retrospective study that included 168 patients with locally advanced or advanced NSCLC who had next-generation sequencing (NGS) performed at our institution between January 1, 2021, and October 31, 2023. Based on their genomic profiles, patients were categorized into three groups: EGFR single mutation, EGFR/TP53 co-mutation, and EGFR/KRAS co-mutation. Baseline clinical data were collected, including gender, age, smoking history, histological subtype, clinical stage, ECOG performance status, gene testing results, and treatment regimens. All patients were treated with EGFR tyrosine kinase inhibitors (TKIs) as first-line therapy, including first-, second-, or third-generation agents. Upon disease progression, patients received platinum-based doublet chemotherapy plus immunotherapy as second-line treatment. The primary endpoint was progression-free survival (PFS). Survival curves were generated using the Kaplan-Meier method and compared by log-rank test. Baseline characteristics among the three groups were compared using the chi-square test. Multivariate Cox regression analysis was performed to evaluate independent prognostic factors for PFS by incorporating all baseline clinical variables and gene mutation status into the model. Results: A total of 168 patients were included in the analysis: 36 with EGFR single mutation, 80 with EGFR/TP53 co-mutation, and 52 with EGFR/KRAS co-mutation. There were no statistically significant differences among the three groups with respect to baseline characteristics, including gender, age, smoking history, histological type, clinical stage, and ECOG performance status ( Conclusion: 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