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Review
. 2023 Apr:184:103929.
doi: 10.1016/j.critrevonc.2023.103929. Epub 2023 Feb 10.

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  1 , Lorenzo Belluomini  2 , Annafrancesca Smimmo  3 , Marco Sposito  4 , Alice Avancini  5 , Diana Giannarelli  6 , Michele Milella  7 , Sara Pilotto  8 , Emilio Bria  9
Affiliations
Free article
Review

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 et al. Crit Rev Oncol Hematol. 2023 Apr.
Free article

Abstract

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.

Keywords: EGFR; NSCLC; Prognostic factor; TP53.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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