Introduction Despite initial benefit, virtually all patients suffering from EGFR-mutant NSCLC experience acquired resistance to tyrosine kinase inhibitors (TKIs), driven by multiple mechanisms. Recent reports have identified oncogenic kinase fusions as off-target resistance mechanisms; however, these alterations have been rarely investigated at EGFR TKIs progression. Results Six gene fusions were detected in tumor progression biopsies under an EGFR TKI from 62 consecutive patients (9.7%) with EGFR-mutated advanced NSCLC. Among 31 patients progressing to first- or second-generation EGFR TKIs, one (3%) had an Eukaryotic translation initiation factor 4 gamma 2–GRB2 associated binding protein 1 (EIF4G2-GAB1) fusion. Among 31 patients progressing to the third-generation osimertinib, five (16%) presented oncogene fusions of fibroblast growth factor receptor 3–transforming acidic coiled-coil containing protein 3 (FGFR3-TACC3) (n = 2), kinesin family member 5B–Ret proto-oncogene (KIF5B-RET) (n..... READ ARTICLE
JTO Clinical and Research Reports DOI:10.1016/j.jtocrr.2020.100023
Authors: Diego Enrico, Ludovic Lacroix, Jeanne Chen, Etienne Rouleau, Jean-Yves Scoazec, Yohann Loriot, Lambros Tselikas, Cécile Jovelet, David Planchard, Anas Gazzah, Laura Mezquita, Maud Ngo-Camus, Stefan Michiels, Christophe Massard, Gonzalo Recondo, Francesco Facchinetti, Jordi Remon, Jean-Charles Soria, Fabrice André, Gilles Vassal, Luc Friboulet, Benjamin Besse