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 III trial of gefitinib versus placebo (TRANS-COG) (2014)

Type of publication:
Conference abstract

Petty R.D., Dahle-Smith A., Miedzybrodzka Z., Dutton S.J., Murray G.I., Stevenson D., *Massie D., Osbourne A., Clark C., Mansoor W., Thompson J., Harrison M., Chatterjee A., Falk S., Elyan S., Garcia-Alonso A., Fyfe D.W., Chau I., Collinson D., Ferry D.

Journal of Clinical Oncology, May 2014, vol./is. 32/15 SUPPL. 1, 0732-183X (20 May 2014)

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 patients only. Results: EGFR FISH results were available for 295 patients. Clinical features were not different from the COG trial . EGFR CNG was found in 46/295 (15.6%). There was no significant correlation with EGFR CNG and any clinical features which were also balanced in G and P groups. In EGFR CNG Pts OS was improved with G compared to P (HR=0.53 95%CI 0.28, 0.98 p=0.042), with survival for G vs P 71 vs 64% ,38 vs 14% , 25 vs 5% and 13 vs 0% at 3 ,6, 9, and 12 months respectively. There was no difference in OS for G vs P in EGFR No CNG pts (HR=0.892 95%CI 0.69, 1.16 p=0.395). For PFS EGFR CNG pts, HR=0.58, 95%CI 0.30, 1.07 p=0.080 for G vs P and HR=0.83 95% CI 0.64, 1.07,p=0.144 for EGFR No CNG pts. DCR was improved for G in EGFR CNG pts(42 vs 13%, p=0.035), and less so for EGFR No CNG (24 vs 14 %, p=0.053). EGFR amplification(6%) pts gained greatest benefit from G ( OS, HR=0.19 95%CI 0.05, 0.65 p=0.007). Conclusions: EGFR CNG identified a subgroup of EC who benefit from Gefitinib as a second line treatment and is a useful predictive biomarker for the first stratified treatment approach in this setting and also a subgroup that may be responsive to other anti-EGFR therapies.

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