Although the introduction of HER2 directed therapy including trastuzumab, pertuzumab, lapatinib, and TDM-1 in the treatment of HER2-positive metastatic breast cancer (mBC) patients favorably changed the natural history of this disease, HER2-positive mBC will eventually progress in most patients. Poziotinib is a novel, oral pan-HER kinase inhibitor which showed potent anti-tumor activities through irreversible inhibition of HER family tyrosine kinases.
This open-label, multicenter phase 2 study was designed to evaluate the efficacy and safety of poziotinib monotherapy in patients with HER2-positive mBC who have progressed from more than 2 HER2-directed therapies. Patients received poziotinib 12 mg once daily on a 14-day on/7-day off schedule. Dose escalation up to 16 mg was allowed at appropriate time point and dose reduction to 8-10 mg were performed according to toxicities. Progression-free survival (PFS) as the primary endpoint and objective response rate (ORR), overall survival (OS), and safety were evaluated.
From Apr 2015 to Feb 2016, 106 patients were enrolled in the trial from 7 institutes in Korea. The patients were median age of 50 (range: 30∼76) who had received median 4 prior anti-cancer therapies including median 2 HER2-directed therapies in the advanced or metastatic setting. Median follow up duration was 12 months. The median PFS was 4.04 months (95% CI, 2.94 - 4.40 months), and median overall survival has not been reached. The disease control rate was 75.49% (77/102) including 20 patients with confirmed partial response. The most common treatment-related AEs were (total/grade≥3) diarrhea (96.23%/14.15%), stomatitis (92.45%/12.26%), and rash (63.21%/3.77%).
Poziotinib showed meaningful clinical activity in heavily-treated HER2-positive mBCs. Diarrhea and stomatitis were the major toxicities leading to dose modification. Biomarker study being analyzed from pre- and on-treatment biopsies is warranted to support further on the meaningful clinical outcomes of poziotinib in HER2-positive mBC.
Clinical trial identification
Legal entity responsible for the study
National OncoVenture & Hanmi Pharmaceutical Co., Ltd.
Hanmi Pharmaceutical Co., Ltd.
All authors have declared no conflicts of interest.