Meta-analysis of the prognostic impact of TP53 co-mutations in EGFR-mutant advanced non-small-cell lung cancer treated with tyrosine kinase inhibitors

Purpose: To assess the prognostic impact of TP53 mutations in EGFR-mutant advanced NSCLC patients treated with TKIs. Methods: Studies exploring the clinical outcomes of EGFR mutant/TP53 wild-type versus EGFR/TP53 co-mutant patients treated with TKIs were selected. Data were cumulated by adopting a fixed and random-effect model. Results: Overall, 29 trials were eligible. The PFS analysis showed that TP53 co-mutant group has shorter PFS versus EGFR mutant/TP53 wild-type group (HR = 1.67, 95% CI 1.51-1.83, heterogeneity I2 =20%, p = 0.18). Patients affected by EGFR/TP53 co-mutant NSCLC have a higher chance of shorter OS versus EGFR mutant/TP53 wild type (HR= 1.89, 95% CI 1.67-2.14, heterogeneity I2 = 21%; p = 0.19). The subgroup analysis showed no significant difference between first-second versus third-generation TKIs in both PFS and OS (p = 0.31, p = 0.08). Conclusions: TP53 mutations represent a clinically relevant mechanism of resistance to EGFR-TKIs, regardless of their generation. A personalized therapeutical approach should be explored in dedicated clinical trials.