As reported by Petty et al in the Journal of Clinical Oncology, analysis of outcomes in the UK phase III Cancer Esophagus Gefitinib trial showed an overall survival benefit with second-line gefitinib (Iressa) in patients with advanced esophageal cancer who had epidermal growth factor receptor (EGFR) copy number gain on fluorescent in situ hybridization.
The phase III trial, reported in 2014, showed no difference in overall survival but significantly improved progression-free survival with gefitinib vs placebo in patients progressing after chemotherapy. The current study was a prespecified blinded molecular analysis of trial tumors comparing overall survival with gefitinib vs placebo in 340 patients with available biomarker data (76% of total population) according to EGFR copy number gain and EGFR, KRAS, BRAF, and PIK3CA mutation status. EGFR copy number gain was determined by fluorescent in situ hybridization using prespecified criteria, with EGFR fluorescent in situ hybridization–positive status being defined as high polysomy or amplification.
Among the 20.2% of patients with EGFR fluorescent in situ hybridization–positive tumors (high polysomy in 13%, amplification in 7.2%), the hazard ratio (HR) for overall survival for gefitinib vs placebo was 0.59 (P = .05). The greatest treatment effect for gefitinib was in the subgroup with EGFR amplification (HR = 0.21, P = .006). No significant benefit of gefitinib was observed among patients with EGFR fluorescent in situ hybridization–negative tumors (HR = 0.90, P = .46), according to the presence of EGFR, KRAS, BRAF, and PIK3CA mutations or for presence of any mutation vs no mutations.
The investigators concluded: “EGFR [copy number gain] assessed by [fluorescent in situ hybridization] appears to identify a subgroup of patients with esophageal cancer who may benefit from gefitinib as a second-line treatment. Results of this study suggest that anti-EGFR therapies should be investigated in prospective clinical trials in different settings in EGFR [fluorescent in situ hybridization]-positive and, in particular, EGFR-amplified esophageal cancer.”
The study was supported by the Scottish Government, Grampian Gastroesophageal Cancer Research Fund, and UK National Health Service.
Russell D. Petty, MBChB, PhD, of the University of Dundee School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
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