Meta-analysis of the prognostic impact of TP53 co-mutations in EGFR-mutant advanced non-small-cell lung cancer treated with tyrosine kinase inhibitors
Miriam Grazia Ferrara, Lorenzo Belluomini, Annafrancesca Smimmo, Marco Sposito, Alice Avancini, Diana Giannarelli, Michèle Milella, Sara Pilotto, Emilio Bria
Abstract
To assess the prognostic impact of TP53 mutations in EGFR -mutant advanced NSCLC patients treated with TKIs. 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. 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 I 2 =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 I 2 = 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 ). 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. • TP53 mutations, impact on responsiveness to EGFR-TKIs. • EGFR/TP53 co-mutation negatively affects OS and PFS regardless of TKIs generation. • EGFR/TP53 co-mutant NSCLC should probably be considered a distinct disease subgroup.