Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors.
- Author:
Tae Min KIM
1
;
Keun Wook LEE
;
Do Youn OH
;
Jong Seok LEE
;
Seock Ah IM
;
Dong Wan KIM
;
Sae Won HAN
;
Yu Jung KIM
;
Tae You KIM
;
Jee Hyun KIM
;
Hyesun HAN
;
Woo Ho KIM
;
Yung Jue BANG
Author Information
- Publication Type:Original Article
- Keywords: EGFR mutation; HER2 amplification; Poziotinib; Non-small-cell lung carcinoma
- MeSH: Anorexia; Appointments and Schedules; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Cohort Studies; Diarrhea; Epithelial Cells; Humans; In Vitro Techniques; Lung; Maximum Tolerated Dose; Pharmacokinetics; Phosphotransferases; Protein-Tyrosine Kinases*; Pruritus; Receptor, Epidermal Growth Factor; Stomach Neoplasms; Stomatitis; Tyrosine*
- From:Cancer Research and Treatment 2018;50(3):835-842
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors. MATERIALS AND METHODS: Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort. RESULTS: A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Dose-limiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer). CONCLUSION: Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.
