Effect of EGFR-TP53 co-mutation on the efficacy of EGFR-TKIs in patients with advanced NSCLC and therapeutic strategies: A retrospective study

This study aimed to describe the therapeutic efficacy and clinical outcomes of patients with advanced non-small cell lung cancer harboring both EGFR mutation and TP53 co-mutations compared to those with only EGFR mutation (TP53 wild-type) when treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and explore strategies to optimize treatment approaches for patients with EGFR-TP53 co-mutation. Demographic information and clinical data of target population were collected for analysis. Forty-six patients who met the specified criteria included 20 patients with EGFR mutation and TP53 wild-type and 26 patients with EGFR-TP53 co-mutation. The objective response rate of the EGFR-TP53 co-mutant group and EGFR mutation TP53 wild-type group was 46.2% versus 75.0% ( P  = .049); median PFS (mPFS) was 8.0 months vs 18.0 months ( P  = .009); and mOS was 11.0 months versus 31.0 months ( P  = .021). The mPFS of the EGFR-TP53 co-mutants receiving gefitinib and osimertinib as first-line therapy was 3.0 months versus 9.0 months ( P  = .022) and mOS was 6.0 months versus 12.0 months ( P  = .041). The mOS of the EGFR-TP53 co-mutant group who received second-line TKIs combined with platinum-containing double-drug chemotherapy and bevacizumab after the progression of first-line single-drug TKIs was 27.0 months versus 6.0 months compared with those who did not receive second-line therapy ( P  = .019). TP53 mutations can significantly negatively affect the efficacy of EGFR-TKIs in patients with advanced non-small cell lung cancer with EGFR mutation. In first-line EGFR-TKIs monotherapy in patients with EGFR-TP53 co-mutation, osimertinib was clearly superior to gefitinib. In first-line EGFR-TKIs monotherapy progression, TKIs combined with chemotherapy and antiangiogenesis therapy could prolong patients’ survival.