About 10% of the patients with non-small cell lung cancer (NSCLC) suffer from EGFR exon 20 insertion. There are currently no effective drugs for EGFR exon 20 insertion, resulting in poor prognosis. Poziotinib is a tyrosine kinase inhibitor (TKI) that inhibits pan-HER signaling pathway, including HER1 (erbB1; EGFR), HER2 (erbB2), and HER4 (erbB4). Spectrum Pharmaceuticals, an American biotechnology company, showed the preliminary analysis of phase II clinical trial of poziotinib at the 18th World Conference on Lung Cancer (WCLC). 11 NSCLC patients with EGFR exon 20 insertion received poziotinib at a 16mg daily dose. 8 (73%) of the 11 patients achieved a partial response and showed efficacy in patients with central nervous system metastases. Toxicities have described for other TKIs and poziotinib that included rash, diarrhea, paronychia, and mucositis led to dose reduction in 6 (55%) of 11 patients. Furthermore, this phase II trial is still in progress. These results revealed that poziotinib has the potential to provide clinical benefit for NSCLC patients with EGFR exon 20 insertion and CNS metastases.