Concurrent TP53 mutations predict a poor prognosis of EGFR-mutant NSCLCs treated with TKIs: An updated systematic review and meta-analysis

The prognostic value of tumor protein P53 (TP53) mutation for tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant non-small-cell lung cancer (NSCLC) remains controversial. Therefore, the present meta-analysis was performed to investigate the potential association between the prognosis of TKI treatment for patients with advanced EGFR mutation-positive NSCLC and the presence or absence of concurrent TP53 mutations. In the present study, 24 eligible studies from the PubMed, Embase and Cochrane databases were identified by screening prior to inclusion. Data were extracted by two independent investigators and analyzed using STATA 14.0 software. Pooled odds ratios (ORs) with 95% confidence interval (CIs) were used to determine the association between objective response rates (ORRs) and TP53 mutations. In addition, differences in the incidence of TP53 mutations between patients with exon 21 L858R mutations and exon 19 deletions of EGFR were evaluated using this method. Pooled hazard ratios (HRs) with 95% CIs were used to calculate the prognostic value of TP53 mutations for progression-free survival (PFS) and overall survival (OS). No significant difference in the incidence of TP53 mutations was detected between the patients with exon 21 L858R mutation and those with exon 19 deletion (OR=0.91; 95% CI=0.65-1.27; P=0.568). However, the pooled results revealed that TP53 mutations were significantly associated with shorter PFS (HR=1.51; 95% CI=1.33-1.71; P<0.001) and OS (HR=1.64; 95% CI=1.33-2.02; P<0.001). By contrast, TP mutations were not associated with the ORR of EGFR-TKI treatment (OR=0.91; 95% CI=0.69-1.21; P=0.529). In conclusion, a worse prognosis for TKI treatment was observed in patients with EGFR-mutant NSCLCs and concurrent TP53 mutations, suggesting that TP53 mutations is associated with primary resistance to EGFR-TKIs.