A Comprehensive Review of Epidermal Growth Factor Receptor Mutation Abundance in Non-Small Cell Lung Cancer Treated with Tyrosine Kinase Inhibitors.

Abstract

Background: Lung cancer is a major contributor to cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are currently viewed as the established first-line therapy for patients with advanced NSCLC with EGFR mutations.

Summary: The potential predictive value of the quantitative abundance of epidermal growth factor receptor (EGFR) mutations in the treatment of NSCLC is widely recognized and regarded as a significant indicator. The definition of mutation abundance in the EGFR gene in most current studies is mainly calculated based on the ratio of mutation to wild-type gene copy number or based on the ratio of allele number; for example, variant allele frequency is the ratio of the number of mutant alleles to the total number of alleles at a particular locus. Results of the included primary studies are as follows. (1) Significant association between EGFR mutation abundance and progression-free survival (PFS): median PFS was significantly longer in the high abundance group (11.0 months, 95% CI: 9.7-12.3 months) than in the low abundance group (5.3 months, 95% CI: 3.6-7.0 months) in the study by Liu et al. High mutation abundance (HR: 0.77, 95% CI: 0.66-0.82, p = 0.037) was an independent prognostic determinant of PFS in the study by Wang et al. Among patients receiving EGFR-TKI as first-line therapy, the median PFS was significantly longer in the high mutation abundance group than in the low mutation abundance group (12.7 months vs. 8.7 months, p = 0.002). EGFR mutation abundance ≥30% was an independent risk factor for PFS (HR: 1.64, 95% CI: 1.17-2.31). (2) Significant association between EGFR mutation abundance and overall survival (OS): the median OS in the high abundance group in the study by Liu et al. was 20.9 months (95% CI: 18.3-23.5 months), while that in the low abundance group was 13.0 months (95% CI: 10.0 months) (95% CI: 10.3-15.7 months); longer OS was independently associated with high mutation abundance (HR: 0.62, 95% CI: 0.50-0.79, p = 0.027).

Key messages: The objective of this article was to conduct a comprehensive examination and analysis of the association between the abundance of EGFR mutations in NSCLC and the effectiveness of treatment with TKIs while also considering the development of drug resistance.