title: Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study.
abstract: Epidermal growth factor receptor (EGFR) has been reported to be overexpressed and amplified in a high percentage of patients with esophageal squamous cell carcinoma (ESCC). The activity of icotinib, an EGFR tyrosine kinase inhibitor, was assessed in previously treated ESCC with EGFR overexpression or amplification.
  
  
  
  For this phase 2, single-arm, multicenter trial undertaken at six hospitals in China, we included Chinese patients with previously treated, histologically confirmed advanced ESCC and EGFR overexpression (immunohistochemical staining sore of 3+) or amplification (positive fluorescence in situ hybridization result). These patients received oral icotinib (250 mg, three times daily).The primary end point was the proportion of patients with objective responses as assessed by an independent radiology review committee.
  
  
  
  Between December 5, 2013, and May 28, 2015, a total of 281 patients were screened. Fifty-four eligible patients were enrolled. Nine responses were observed, including one complete response and eight partial responses, and 16 patients had stable disease, resulting in a 16.7% objective response rate (95% confidence interval [CI]: 6.7-26.6) and 46.3% disease control rate (95% CI: 33.0-59.6). The median progression-free survival and overall survival times were 52 (95% CI: 40-95) days and 153 (95% CI: 139-218) days, respectively. A total of 43 patients experienced at least one adverse event, but most were only grade 1 to 2 in severity. The most frequent was rash (48.1%), followed by diarrhea (22.2%).
  
  
  
  Icotinib showed favorable activity in patients with advanced, previously treated ESCC with EGFR overexpression or amplification. These findings suggest further research into EGFR overexpression or amplification for selecting responsive patients.
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Oncology, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Pathology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ying
authors.affiliation: Department of Medical Oncology, Chifeng Municipal Hospital, Chifeng, People's Republic of China.
authors.forename: Changwu
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Henan Cancer Hospital, Zhengzhou, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Betta Pharmaceuticals Co., Ltd, Hangzhou, People's Republic of China.
authors.forename: Fenlai
authors.initials: F
authors.lastname: Tan
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address: suny@csco.org.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D043844:Crown Ethers / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D043844:Crown Ethers; D011799:Quinazolines; C531470:icotinib; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR amplification; EGFR overexpression; Esophageal carcinoma; Icotinib; Squamous cell carcinoma