Abstract 1229P
Background
Co-mutations of genes, such as RB1, LKB1, have been reported to influence the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with mutated EGFR.However, whether DNA damage repair (DDR) genes co-mutations have an impact on the efficacy of EGFR-TKIs in EGFR mutated NSCLC patients were still obscure.
Methods
Next-generation sequencing (NGS) data of NSCLC patients was obtained from cBioPortal (www.cbioportal.org). Relationship of EGFR activating mutations and DDR gene mutations were listed in a heatmap. To explore the association between DDR pathways and the clinical benefit of EGFR-TKIs, we included genomic and clinical data from our clinical practice. The included patients were divided into four cohorts: Cohort 1, EGFR+DDR+ receiving first generation EGFR-TKIs; Cohort 2, EGFR+DDR- receiving first generation EGFR-TKIs; Cohort 3, EGFR+DDR+ receiving first generation EGFR-TKIs combined with antiangiogenic agents (A+T); Cohort 4, EGFR+DDR- receiving A+T. Survival analysis was performed using Kaplan-Meier curves.
Results
A total of 158 EGFR-mutated NSCLC sequencing data from cBioPortal were included. The incidence DDR genes mutation was found in 82.05% NSCLC patients with EGFR mutations. (Figure 1) In addition, 40 EGFR mutated NSCLC patients, with DDR genes sequencing information, were included for efficacy analysis. The efficiency results showed the median progression free survival (mPFS) of patients with EGFR+/DDR+ and EGFR+/DDR- receiving EGFR-TKIs were 6.3 months (cohort 1) and 12.0 months (cohort 2) respectively; and the mPFS of patients with EGFR+/DDR+ and EGFR+/DDR- receiving A+T regimens were 15.0 months (cohort 3) and NR months (cohort 4) respectively. (Figure 2).
Conclusions
Co-mutation of DDR genes influence the efficiency of EGFR-TKIs in NSCLC patients harboring EGFR activating mutations. Combing antiangiogenic agents with EGFR-TKIs may be a promising way to improve the efficiency NSCLC patients with EGFR+/DDR+.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.