Role of HER2 copy number amplification and PI3K pathway as a biomarker for patients with HER2+ MBC treating with Poziotinib, pan-HER TKI.

e13009Background: A phase II clinical trial of poziotinib, a pan- human epidermal growth factor receptor(HER) kinase inhibitor, demonstrated anti-tumoral activity of poziotinib among patients with heavily treated HER2+ metastatic breast cancer(MBC). We performed the exploratory analysis of the impact of genetic alterations of HER2 and PIK3CA pathway on the efficacy of poziotinib in this trial. Methods: All participants were diagnosed as HER2+ breast cancers (BCs) and provided tissue specimens. We performed targeted ultra-deep sequencing with a customized cancer gene panel (CancerSCAN™) and nConuter expression assay. We analyzed the relationship between the sequencing data and clinical outcome. Results: From Apr 2015 to Feb 2016, 106 patients were enrolled in the trial from 7 institutes in Korea. Of 106 patients, biomarker data were available for 85 patients. Of 85 patients, copy number(CN) amplifications of HER2 were observed in 72 patients (85%) and CN > 4(log scale) were in 34(40%). Single nucleotide va...