A comprehensive overview of the heterogeneity of EGFR exon 20 variants in NSCLC and (pre)clinical activity to currently available treatments

Fenneke Zwierenga*, Bianca A M H van Veggel, Anke van den Berg, Harry J M Groen, Lili Zhang, Matthew R Groves, K Kok, E F Smit, T Jeroen N Hiltermann, Adrianus J de Langen, Anthonie J van der Wekken

*Bijbehorende auteur voor dit werk

Onderzoeksoutputpeer review

1 Citaat (Scopus)
58 Downloads (Pure)


Activating EGFR mutations are commonly observed in non-small cell lung cancer (NSCLC). About 4-10 % of all activating epidermal growth factor receptor (EGFR) mutations are heterogenous in-frame deletion and/or insertion mutations clustering within exon 20 (EGFRex20+). NSCLC patients with EGFRex20+ mutations are treated as a single disease entity, irrespective of the type and location of the mutation. Here, we provide a comprehensive assessment of the literature reporting both in vitro and clinical drug sensitivity across different EGFRex20+ mutations. The activating A763_Y764insFQEA mutation has a better tumor response in comparison with mutations in the near- and far regions directly following the C-helix and should therefore be treated differently. For other EGFRex20+ mutations marked differences in treatment responses have been reported indicating the need for a classification beyond the exon-based classification. A further classification can be achieved using a structure-function modeling approach and experimental data using patient-derived cell lines. The detailed overview of TKI responses for each EGFRex20+ mutation can assist treating physicians to select the most optimal drug for individual NSCLC patients.

Originele taal-2English
Aantal pagina's10
Vroegere onlinedatum19-sep.-2023
StatusPublished - nov.-2023

Citeer dit