The prognostic impact of TP53 comutation in EGFR mutant lung cancer patients: a systematic review and meta-analysis

Abstract

Background The prognostic value of TP53 commutation in epidermal growth factor receptor (EGFR) mutant lung cancer is controversial and we therefore conducted this systematic review and meta-analysis. Methods A systematic search was carried out in Pubmed, Web of Science, the Cochrane Library, Medline and Embase up to 19 April 2018. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS), the relative risk (RR) of objective response rate (ORR) were calculated. Results Overall, a total of eight studies comprising 2979 patients were included. When generally comparing TP53 mutation group with TP53 wild-type group, we confirmed the prognostic value of poor OS of TP53 in EGFR mutant lung cancers (HR 1.73, 95% CI 1.22-2.44, P = 0.002). In subgroup analysis of OS, the prognostic value was maintained in patients treated with EGFR tyrosine kinase inhibitors (TKIs) but not in those treated with non-targeted therapy (HR 2.29, 95% CI 1.39-3.76, P = 0.001), and was also maintained in patients with advanced-stage lung cancers rather than those of all stages (HR 2.00, 95% CI 1.11-3.61, P = 0.021). For patients treated with EGFR TKIs, TP53 commutation was predictive of a poor PFS (HR 2.18, 95% CI 1.42-3.36, P < 0.001) but the prognostic value on ORR was not observed (RR 1.15, 95% CI 0.92-1.44, P = 0.212). Additional subgroup analysis based on TP53 mutation subtypes was not pooled due to limited data. Conclusion Generally we confirmed the prognostic value of poor OS and PFS of TP53 commutation in EGFR mutant lung cancers, and it should be further investigated and validated regarding the prognostic role of TP53 mutation subtypes.

Keywords: Lung cancer; TP53; epidermal growth factor receptor; prognosis.