genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib.
Patients and Methods: A pre-specified blinded molecular analysis of COG trial tumours was conducted to compare efficacy of gefitinib to placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF and PIK3CA mutation status. EGFR CNG was determined by fluorescent insitu hybridisation (FISH) using pre-specified criteria and EGFR FISH positive defined as high polysomy or amplification.
Results: Biomarker data were available for 340 patients. In EGFR FISH positive tumours (20.2%) overall survival was improved with gefitinib compared to placebo (hazard ratio [HR] for death, 0.59; 95% confidence interval [CI], 0.35, 1.00 p=0.05). In EGFR FISH negative tumours there was no difference in overall survival with gefitinib compared to placebo (HR for death, 0.90, 95% CI 0.69,
1.18 p=0.46). EGFR amplification (7.2%) patients gained greatest benefit from gefitinib (HR for death, 0.21; 95% CI 0.07-0.64; p=0.006). There was no difference in overall survival for gefitinib versus placebo for patients with EGFR, KRAS, BRAF and PIK3CA mutations, or for any mutation versus none.
Conclusion: EGFR CNG assessed by FISH appears to identify a subgroup of esophageal cancer patients who may benefit from gefitinib as a second line treatment, and suggests that anti-EGFR therapies should be investigated in prospective clinical trials in different settings in EGFR FI SH positive, and in particular EGFR amplified, esophageal cancer.
FingerprintDive into the research topics of 'Gefitinib and <i>EGFR </i>Gene Copy Number Aberrations in Esophageal Cancer'. Together they form a unique fingerprint.
- School of Medicine, Medical Sciences & Nutrition, Centre for Health Data Science
- Clinical Medicine
- School of Medicine, Medical Sciences & Nutrition, Data Safe Haven
- School of Medicine, Medical Sciences & Nutrition, Applied Medicine - Personal Chair (Clinical)
- Institute of Medical Sciences
Person: Academic, Clinical Academic