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Meta-Analysis
. 2020 Apr:85:101994.
doi: 10.1016/j.ctrv.2020.101994. Epub 2020 Feb 21.

The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: A systematic review and critical appraisal

Valerio Gristina  1 , Umberto Malapelle  2 , Antonio Galvano  1 , Pasquale Pisapia  2 , Francesco Pepe  2 , Christian Rolfo  3 , Silvia Tortorici  4 , Viviana Bazan  5 , Giancarlo Troncone  2 , Antonio Russo  6
Affiliations
Meta-Analysis

The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: A systematic review and critical appraisal

Valerio Gristina et al. Cancer Treat Rev. 2020 Apr.

Abstract

Uncommon epidermal growth factor receptor (EGFR) mutations collectively account for 10% of EGFR mutations, harboring heterogeneous molecular alterations within exons 18-21 with clinically variable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced Non-Small Cell Lung Cancer (NSCLC) patients. In addition, with the introduction of different NGS gene approach an improvement of EGFR mutations detection was reported. Today, no specific studies have prospectively evaluated uncommon sensitizing mutations in detail and no firm standard of care has been established in the first-line setting. The aim of this comprehensive review is to critically consider the clinical role of uncommon EGFR mutations highlighting the results of several in vitro and in vivo studies, which singly evaluated the sensitivity of uncommon mutations to currently European of Medicines Agency (EMA)-approved EGFR TKIs in cell lines, xenograft models and humans, in order to obtain a practical guide for refining the clinical decision-making process.

Keywords: EGFR; NGS; NSCLC; Systematic review; TKIs; Uncommon mutations.

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Conflict of interest statement

Declaration of Competing Interest Dr. Malapelle reports personal fees from Boehringer Ingelheim, AstraZeneca, Roche, MSD, Amgen, Merck, BMS for participation in a speaker bureau; personal fees from Boehringer Ingelheim, MSD, Amgen, Merck, BMS for acting in an advisory role, financial support from Boehringer Ingelheim and Amgen that was paid directly to his institution outside the submitted work. Prof. Rolfo reports personal fees from Merck Sharp and Dohme, Astrazeneca, for participation in a speaker bureau; personal fees from Mylan, Archer, Merck Serono, Inivata for acting in an advisory scientific role; and has research collaborations with Biomarkers and Guardant Health outside the submitted work. Prof. Troncone reports personal fees from Roche for participation in a speaker bureau; personal fees from MSD, Pfizer for acting in an advisory role. The remaining authors declare no potential conflicts of interest.