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Meta-Analysis
. 2022 Jan;26(1):7-18.
doi: 10.1007/s40291-021-00563-1. Epub 2021 Nov 23.

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

Barbara Melosky  1 , Kato Kambartel  2 , Maik Häntschel  3   4 , Margherita Bennetts  5 , Dana J Nickens  6 , Julia Brinkmann  7 , Antonin Kayser  7 , Michael Moran  7   8 , Federico Cappuzzo  9
Affiliations
Meta-Analysis

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

Barbara Melosky et al. Mol Diagn Ther. 2022 Jan.

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.

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Conflict of interest statement

BM reports receiving honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, and Pfizer. KK declares no conflicts of interest. MH reports receiving advisory fees/honoraria from BMS GmbH & Co. KG, Boehringer Ingelheim, Chugai Pharma Germany GmbH, Pfizer Pharma GmbH, and Roche Pharma AG, and grants for scientific research from AstraZeneca. MB is a Pfizer employee and may hold Pfizer stock. DJN is a Pfizer employee and may hold Pfizer stock. JB is a Pfizer employee and may hold Pfizer stock. AK is a Pfizer employee and may hold Pfizer stock. MM was a Pfizer employee at the time of preparation of the publication and may hold Pfizer stock. He is currently an employee of AbbVie and owns stock in AbbVie. FC reports being a consultant and participating in advisory boards for AstraZeneca, Bristol Myers Squibb, Eli Lilly, MSD, Pfizer, Roche, and Takeda.

Figures

Fig. 1
Fig. 1
Flow diagram of the selection of studies included in this meta-analysis. EGFR epidermal growth factor receptor
Fig. 2
Fig. 2
Final model estimates for the All EGFR mutation analysis with percent male covariate. Blue symbols indicate observed data. CI confidence interval, EGFR epidermal growth factor receptor
Fig. 3
Fig. 3
Final model estimates for the exon 19 deletion EGFR submutation analysisa. Blue symbols indicate observed data. aRelative to the overall EGFR mutation population. CI confidence interval, EGFR epidermal growth factor receptor
Fig. 4
Fig. 4
Final model estimates for the exon 21 L858R substitution EGFR submutation analysisa. Blue symbols indicate observed data. aRelative to the overall EGFR mutation population. CI confidence interval, EGFR epidermal growth factor receptor
See this image and copyright information in PMC

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