The following is the summary of “Impact of TP53 Mutations on EGFR-Tyrosine Kinase Inhibitor Efficacy and Potential Treatment Strategy” published in the January 2023 issue of Clinical Lung Cancer by Fu, et al.


Researchers looked into how TP53 mutation risk factors affect the effectiveness of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors and other therapy options. The patient’s baseline characteristics and tumor samples were gathered for next-generation sequencing gene mutation screening. In addition, interval computed tomography scans were used at each follow-up time point to assess the overall response to treatment with Tyrosine kinase inhibitors. The statistical differences in this study were determined using a combination of the log-rank test and Fisher’s exact test.

There were a total of 1,134 clinical samples from patients with early non-small cell lung cancer(NSCLC); of those, TP53mut was found in 644, and EGFRmut in 622. Patients whose tumors were treated with TKIs had a better prognosis if they had a high EGFR co-mutation rate or a low frequency of TP53mut. Furthermore, TP53mut outside the DB domain demonstrated the largest connection with TKI resistance, whereas different TP53mut mutations in the DB domain simply affected progression-free survival(PFS). Patients with prognosis TP53mut benefited more from the combination of EGFR-TKIs and chemotherapy, according to a grouping analysis of EGFR-TKI-based treatment, while EGFR-TKI therapy was beneficial for TP53wt patients. 

Moreover, TP53mut may hasten the relapse of postoperative individuals who otherwise respond favorably to EGFR-TKIs in combination with chemotherapy. The prognosis of patients treated with TKIs is affected in different ways by the features of TP53mut. Combining EGFR-TKIs with chemotherapy improved survival in patients with the prognostic TP53mut,  providing a valuable benchmark for the treatment management of EGFRmut patients.

Source: sciencedirect.com/science/article/abs/pii/S1525730422001863