Impact of TP53 Mutations on EGFR-Tyrosine Kinase Inhibitor Efficacy and Potential Treatment Strategy

Background: We investigated the impact of factors that influence TP53 mutations on the efficacy of EGFR-tyrosine kinase inhibitors and potential treatment strategies.

Materials And Methods: Tumor samples were collected to screen gene mutations by next-generation sequencing, as well as the patients' baseline characteristics. The overall response to treatment with TKIs was evaluated based on interval computed tomography scans at each follow-up time point. A Fisher's exact test and log-rank test were used to determine the statistical differences in this study.

Results: A total of 1134 clinical samples were collected from NSCLC patients, and TP53 was identified in 644 cases and EGFR in 622 cases. A low frequency of TP53 or more than 50% EGFR co-mutation rate were related to the prognosis of TKI-treated patients. In addition, TP53 in the region outside of the DB domain had the strongest correlation with TKI resistance, whereas various types of mutations in the DB domain only had an impact on PFS. A grouping study of EGFR-TKI-based treatment revealed that EGFR-TKIs with chemotherapy were associated with more significant survival benefits for patients with prognostic TP53, whereas EGFR-TKI therapy was favorable for TP53 patients. Furthermore, TP53 could shorten the time to the relapse of postoperative patients, who will also likely respond well to EGFR-TKIs with chemotherapy.

Conclusion: Various characteristics of TP53 affect the prognosis of TKI-treated patients to varying degrees. EGFR-TKIs with chemotherapy were benefit for patients' survival with prognostic TP53, which provides an important reference for treatment management of EGFR patients.