Poziotinib Shows Clinical Benefit in EGFR Exon 20–Mutant NSCLC, Efficacy Dependent on Insertion Location.
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Poziotinib Shows Clinical Benefit in EGFR Exon 20–Mutant NSCLC, Efficacy Dependent on Insertion Location.

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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