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Table 2 Summary of the selected clinical experiences with different agents targeting Receptor Tyrosine Kinases in ESCC

From: Expression, regulation and targeting of receptor tyrosine kinases in esophageal squamous cell carcinoma

Study Type of the study Number of patients Indication Primary outcomes
i. EGFR-targeting agents:
Dutton et al. (2014) Phase III Total number: 450 patients ESCC: 106 Gefitinib for esophageal cancer progressing after chemotherapy The use of gefitinib as a second-line treatment in esophageal cancer in unselected patients does not improve overall survival (for all patients as well as for both histology subgroups).
Ilson et al. (2011) Phase II Total number: 30 patients ESCC: 13. Erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus Overall, erlotinib had limited activity in patients with esophageal cancer with some responses observed in ESCC.
Rodriguez et al. (2010) Phase II Total number: 173 ESCC: 19 Perioperative concurrent chemotherapy, gefitinib, and hyperfractionated radiation followed by maintenance gefitinib in locoregionally advanced esophagus and gastroesophageal junction cancer. Gefitinib did not worsen CCRT toxicity; maintenance gefitinib proved difficult.
Zhai et al. (2013) Phase II (pilot study) 18 patients Concurrent erlotinib and radiotherapy for chemoradiotherapy-intolerant ESCC patients For ESCC patients who cannot tolerate chemoradiotherapy, concurrent erlotinib and radiotherapy were tolerable and effective.
Huang et al. (2016) Phase II 281 patients Icotinib in Patients with Pretreated Advanced ESCC with EGFR overexpression or EGFR Gene Amplification Overall, icotinib showed favorable activity in patients with advanced, previously treated ESCC with EGFR overexpression or amplification (in terms of response rate, overall survival and progression-free survival).
Janmmat et al. (2006) Phase II Total number: 36 patients ESCC: 9 Gefitinib in second-line treatment of advanced esophageal cancer patients Overall, gefitinib has a modest activity in second-line treatment of advanced esophageal cancer. However, the patient outcome was significantly better in female patients and in patients demonstrating high EGFR expression or ESCC histology.
ii. VEGF/VEGFR-targeting agents:
Janjigan et al. (2015) Phase II Total number: 35 patients ESCC: 5 patients Sorafenib in chemotherapy-refractory esophageal carcinoma For all patients: 8 week Kaplan-Meier estimated progression-free survival (PFS) was 61% (90% CI 45 to 73%). Median PFS was 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months).
Horgan et al. (2016) Phase II Total number: 61 patients ESCC: 12 patients Adjuvant sunitinib following chemoradiotherapy and surgery for locally advanced esophageal cancer For all patients: median survival was 26 months with a 2 and 3-year survival rate of 52% and 35%.