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Phase II trial of dacomitinib in patients with HER2-positive gastric cancer

 Do-Youn Oh  ;  Kewn-Wook Lee  ;  Jae Yong Cho  ;  Won Ki Kang  ;  Seock-Ah Im  ;  Jin Won Kim  ;  Yung-Jue Bang 
 GASTRIC CANCER, Vol.19(4) : 1095-1103, 2016 
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BACKGROUND: Dacomitinib, an irreversible panHER inhibitor, shows significant preclinical antitumor activity in human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC). The aim of this study was to evaluate the clinical activity of dacomitinib and discover potential biomarkers in HER2-positive GC patients.

METHODS: We enrolled previously treated advanced HER2-positive GC [HER2 FISH (+) or HER2 IHC 3+] patients. The patients received dacomitinib 45 mg once daily.

RESULTS: A total of 27 patients were enrolled. The number of prior chemotherapy regimens was 1 in 7 patients (26 %), 2 in 9 patients (33 %), and more than 2 in 11 patients (41 %). Seven patients had received prior anti-HER2 therapy. The 4-month progression-free survival (PFS) rate was 22.2 % and median PFS was 2.1 months (95 % CI, 2.3-3.4) There were 2 partial response (PRs) and 9 stable disease (SDs), resulting in 7.4 % (95 % CI, 0-17.5 %) of response rate (RR) and 40.7 % (95 % CI, 21.9-59.6 %) of disease control rate (DCR). Eleven patients (41 %) showed some degree of tumor shrinkage. Overall survival was 7.1 months (95 % CI, 4.4-9.8). The most common toxicities were skin rash, diarrhea, and fatigue, most of which were grade 1 or 2. The Ctrough of dacomitinib was lower in gastrectomy patients than nongastrectomy patients. Higher serum levels of HER2 extracellular domain (ECD) and lower levels of soluble E-cadherin (sECAD) correlated with higher dacomitinib activity.

CONCLUSIONS: Dacomitinib functions as a single agent in HER2-positive GC patients with a tolerable safety profile. HER2 ECD and sECAD have the potential to be biomarkers for patient selection in a panHER inhibition strategy for HER2-positive GC. (ClinicalTrials.gov: NCT01152853).
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Jae Yong(조재용) ORCID logo https://orcid.org/0000-0002-0926-1819
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