Epidermal growth factor receptor copy number gain (EGFR CNG) and response to gefitinib in esophageal cancer (EC): Results of a biomarker analysis of a phase Ill trial of gefitinib versus placebo (TRANS-COG).

4016 Background: The Cancer Oesophagus Gefitinib (COG) trial randomised (1:1) 450 patients(pts) with advanced EC who had progressed after 1-2 lines of chemotherapy to gefitinib (G) or placebo (P). Improved disease control rates- DCR= RECIST CR+PR+SD at 8 weeks (P 15.6%, G 24.1%, p = 0.016), improved patient reported outcomes, and progression free survival (HR = 0.80, 95%CI 0.66, 0.96, p = 0.020) were seen with G-indicative of rapid and durable responses that were observed in a subset. We hypothesised that EGFR CNG in ECs would identify a subgroup responsive to G. Methods: EGFR CNG was determined by FISH on FFPE tumour specimens(all subject to central pathology review) and performed blind to treatment allocation and outcome. Disomy, low and high trisomy and low polysomy were classified as negative (No CNG) and high polysomy and amplification as positive(CNG). Primary endpoint was OS for G versus P in EGFR CNG and no CNG groups. Secondary endpoints were PFS, DCR and HRQL and outcomes in EGFR amplified patie...