Distribution and Detectability of EGFR Exon 20 Insertion Variants in Non-small Cell Lung Cancer

INTRODUCTION: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations represent 5%-10% of EGFR mutations in non-small cell lung cancer (NSCLC). Identifying patients with EGFR ex20ins is challenging due to the limited coverage of polymerase chain reaction (PCR) assays and the relatively recent use of next-generation sequencing (NGS). This study analyzes the spectrum of EGFR ex20ins variants in a large patient population from a global clinical trial and several real-world cohorts and the ability of PCR kits to identify these alterations. METHODS: We conducted this retrospective analysis in patients with NSCLC who underwent NGS/sequencing testing and had a known EGFR ex20ins mutation. Patients were gathered from a clinical trial (NCT02716116), a chart review study in Germany, and the LC-SCRUM-Japan, GENIE, and US COTA databases. Proportions of patients with ex20ins variants that could have been detected by 6 commercially available and widely used PCR kits were calculated in each dataset. RESULTS: Overall, 636 patients with NSCLC harboring EGFR ex20ins mutations were included in this analysis, and 104 unique EGFR ex20ins variants were identified across the data sources. The proportion of patients whose ex20ins could have been detected by any PCR test alone ranged from 11.8% to 58.9% across the data sources. CONCLUSIONS: Our findings suggest that the PCR tests assessed would have missed >40% of patients with NSCLC harboring EGFR ex20ins mutations. NGS-based genetic testing is preferable over standard PCR assays and can substantially improve the identification of the diverse profile of EGFR ex20ins variants in NSCLC.

• Ignatius Ou, S. H.
• Hong, J. L.
• Christopoulos, P.
• Lin, H. M.
• Vincent, S.
• Churchill, E. N.
• Soeda, J.
• Kazdal, D.
• Stenzinger, A.
• Thomas, M.