20 Aug Poziotinib Shows Clinical Benefit in EGFR Exon 20–Mutant NSCLC, Efficacy Dependent on Insertion Location.
In 50 patients with advanced EGFR exon 20-mutant NSCLC, treatment with poziotinib showed confirmed ORRs of 31% by blinded independent review, with a median PFS of 5.5 months. Preclinical studies, in silico modeling, and molecular dynamics simulations showed that the poziotinib sensitivity was highly dependent on the insertion location, with near-loop insertions (ORR: 46%) being more sensitive than far-loop insertions (ORR: 0%). Putative mechanisms of acquired resistance to poziotinib included EGFR T790M, MET amplifications, and epithelial-to-mesenchymal transition (EMT). (Ref: Elamin YY et al. Cancer Cell. July 2022)
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