Worldwide Prevalence of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis

Abstract

Background Identification of variable epidermal growth factor receptor ( EGFR ) gene mutations in non-small cell lung cancer (NSCLC) is important for the selection of appropriate targeted therapies. This meta-analysis was conducted to provide a worldwide overview of EGFR mutation and submutation (specifically exon 19 deletions, exon 21 L858R substitutions, and others) prevalence, and identify important covariates that influence EGFR mutation status in patients with advanced NSCLC to address this clinical data gap. Methods Embase ® and MEDLINE ® in Ovid were searched for studies published between 2004 and 2019 with cohorts of ≥ 50 adults with EGFR mutations, focusing on stage III/IV NSCLC (≤ 20% of patients with stage I/II NSCLC). Linear mixed-effects models were fitted to EGFR mutation endpoints using logistic transformation (logit), assuming a binomial distribution. The model included terms for an intercept reflecting European studies and further additive terms for other continents. EGFR submutations examined were exon 19 deletions, exon 21 L858R substitutions, and others. Results Of 3969 abstracts screened, 57 studies were included in the overall EGFR mutation analysis and 74 were included in the submutation analysis relative to the overall EGFR mutation population (Europe, n = 12; Asia, n = 51; North America, n = 5; Central America, n = 1; South America, n = 1; Oceania, n = 1; Global, n = 3). The final overall EGFR mutations model estimated Asian and European prevalence of 49.1% and 12.8%, respectively, and included an additive covariate for the proportion of male patients in a study. There were no significant covariates in the submutation analyses. Most submutations were actionable: exon 19 deletions (49.2% [Asia]; 48.4% [Europe]); exon 21 L858R substitutions (41.1% [Asia]; 29.9% [Europe]). Conclusions Although EGFR mutation prevalence was higher in Asian than Western countries, data support worldwide testing for EGFR overall and submutations to inform appropriate targeted treatment decisions. Supplementary Information The online version contains supplementary material available at 10.1007/s40291-021-00563-1.

Clinicopathologic Features and Molecular Biomarkers as Predictors of Epidermal Growth Factor Receptor Gene Mutation in Non-Small Cell Lung Cancer Patients

“…Wei et al [ 12 ] observed no significant differences in gender and smoking status between the two common mutations 19-Del and L858R. In a recent meta-analysis [ 5 ] for NSCLC patients worldwide, the percentage of male patients was a significant covariate for the overall EGFR mutation but not for the mutation subtypes. With the increase of the percentage of males, the EGFR mutation frequency decreased.…”

“…The median ages were also comparable between the EGFR-mutated and wild groups [ 6 , 9 , 23 ]. In a recent meta-analysis, age was not considered as a covariate for the overall EGFR mutation [ 5 ]. Some studies take a different view on the relationship between EGFR mutations and age.…”

“…More and more driver genes have been found in recent years, and the epidermal growth factor receptor (EGFR) gene is the most common one in NSCLC patients. EGFR gene mutation frequency varies in different countries and regions around the world, with the highest frequency (49.1%) in the NSCLC patients of Asian countries compared with other continents (11.9–33.0%) [ 5 ]. EGFR tyrosine kinase inhibitors (EGFR-TKIs) are widely applied to the advanced NSCLC, which lays a foundation for promoting individualized and targeted therapy.…”

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma

“…In NSCLC, the incidence of EGFR mutations varies considerably in different regions of the world. Several studies reported that the prevalence of EGFR mutations ranged from 11% to 50% [ 30 , 31 ]. A large meta-analysis conducted in 2016 including 456 studies showed significant heterogeneity in all analyzed variables related to the prevalence of EGFR mutations in NSCLC patients [ 32 ].…”

Complex EGFR mutations in non-small cell lung cancer: a distinct entity?

“…EGFR-activating mutations are typical for lung adenocarcinomas and are relatively frequent in nonsmokers, females, and East Asian patients. Common (classical) mutations, constituting up to 90% of EGFR mutations, include small in-frame deletions within exon 19 (codons 746-750) and a point mutation within exon 21 (L858R) (1). The remaining EGFR mutations (uncommon; non-classical) may be intrinsic (primary) or secondary, related to acquired resistance to EGFR TKIs (2)(3)(4).…”