Efficacy and safety analyses of epidermal growth factor receptor tyrosine kinase inhibitors combined with chemotherapy in the treatment of advanced non-small-cell lung cancer with an EGFR/TP53 co-mutation

Purpose: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with cytotoxic chemotherapy are highly effective in the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study is to evaluate the efficacy and safety of this combination in advanced NSCLC patients with an EGFR/TP53 co-mutation.

Methods: Ninety-five advanced NSCLC patients with an EGFR/TP53 co-mutation were enrolled in this study. Treatments with either EGFR-TKI monotherapy (T group, n = 61) or EGFR-TKI combined with chemotherapy (TC group, n = 34) were evaluated in relation to objective response rate (ORR), disease control rate (DCR), median time to progression (TTP), and median overall survival (OS).

Results: There were no statistically significant differences in DCR between the treatment groups. The ORR was significantly improved in the TC group versus the T group (55.9% vs. 34.4%, P = 0.042). A higher median TTP was noted in TC group compared with T group (16.1 vs. 11.1 months, P = 0.002). Patients without brain metastases in TC group had a longer median OS than in T group (48.4 vs. 28.8 months, P = 0.003). However, there was a non-significant trend towards longer OS in TC group in the entire cohort (36.9 vs. 28.2 months, P = 0.078). Cox multivariate regression analysis showed that clinical stage, brain metastases, EGFR21 L858R mutation, and T790M status at first progression were independent risk factors for OS. However, the incidence of grade 3 or higher adverse events were higher in the TC group than in the T group (32.4% vs. 13.1%, P = 0.025).

Conclusion: Our study indicates that EGFR-TKIs combined with chemotherapy could significantly improve the ORR and TTP of advanced NSCLC patients with an EGFR/TP53 co-mutation. Combination therapy may be a promising treatment for advanced NSCLC patients with an EGFR/TP53 co-mutation without brain metastases.