title: Phase II trial of dacomitinib in patients with HER2-positive gastric cancer.
abstract: 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).
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Kewn-Wook
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Gangnam Severance Hospital, Seoul, South Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Samsung Medical Center, Seoul, South Korea.
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. bangyj@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. bangyj@snu.ac.kr.
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D052999:Quinazolinones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D052999:Quinazolinones; D018719:Erb-b2 Receptor Tyrosine Kinases; C525726:dacomitinib; C508053:ERBB2 protein, human
keywords: Dacomitinib; Gastric cancer; HER2; HER2 ECD; Soluble E-cadherin