Cited 2 times since 2023 (3 per year) source: EuropePMC Cancer treatment reviews, Volume 120, 19 3 2023, Pages 102628 A comprehensive overview of the heterogeneity of EGFR exon 20 variants in NSCLC and (pre)clinical activity to currently available treatments. Zwierenga F, van Veggel BAMH, van den Berg A, Groen HJM, Zhang L, Groves MR, Kok K, Smit EF, Hiltermann TJN, de Langen AJ, van der Wekken AJ
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.
