Prelaj A, Bottiglieri A, Proto C, et al. - Researchers focused on poziotinib’s (a new generation tyrosine kinase inhibitor) activity and toxicity in metastatic non–small-cell lung cancer (mNSCLC) with EGFR/HER2-exon-20-i-mut (insertion mutation). Participants were patients with NSCLC managed either with EGFR or HER2 exon 20-i-mut within an expanded access program. Patients were given poziotinib (16 mg or less) orally quaque die (QD). A median progression free survival (PFS) of 5.6 months and mOS (overall survival) of 9.5 months was reported. An overall response rate (ORR) of 30% (EGFR/HER2: 23/50%) and disease control rate (DCR) 80% were obtained. Overall, there were impacts of poziotinib in mNSCLC patients with EGFR/HER2-exon 20-i-mut. A high toxicity rate resulted in frequent dose interruption and reduction, thus, decreasing mPFS in cases with good ORR/DCR. To assess the low dose as well as new scheduled dose (e.g. bis in die (BID)), ZENITH20 trial is now being used.