Optimal therapy for concomitant EGFR and TP53 mutated non-small cell lung cancer: A real- world study

Background: Concomitant TP53 mutation results in poor prognosis in patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) and may preferentially benefit from a combination regimen. The present study aims to compare the benefits of EGFR-TKIs and its combination with antiangiogenic drugs or chemotherapy in patients with NSCLC harboring EGFR and TP53 co-mutation in a real-life setting. Methods This retrospective analysis included 124 patients with advanced NSCLC having concomitant EGFR and TP53 mutations, who underwent next-generation sequencing prior to treatment. Patients were classified into the EGFR-TKI group and combination therapy group. The primary endpoint of this study was progression-free survival (PFS). Kaplan–Meier (KM) curves were plotted to analyze PFS, and log-rank test was used to compare differences between groups. Univariate cox regression analysis was performed on the risk factors associated with survival. Results The combination group included 72 patients who received the regimen of EGFR-TKIs combined with antiangiogenic drugs or chemotherapy, while the EGFR-TKI monotherapy group included 52 patients treated with TKI only. The median PFS was significantly longer in the combination group than in the EGFR-TKI group (18.0 months; 95% confidence interval [CI]: 12.1–23.9 vs. 7.0 months; 95% CI: 6.1–7.9; p < 0.001) with greater PFS benefit in TP53 exon 4 or 7 mutations subgroup. Subgroup analysis showed a similar trend. The median duration of response was significantly longer in the combination group than in the EGFR-TKI group. Patients with 19 deletions or L858R mutations both achieved a significant PFS benefit with combination therapy versus EGFR-TKI alone. Conclusions Combination therapy had a higher efficacy than EGFR-TKI alone for patients with NSCLC having concomitant EGFR and TP53 mutations. Future clinical trials are needed to determine the role of combination therapy for this patient population.