Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA)

Abstract

The aim of this study was to evaluate the usefulness of EGFR mutation status in serum DNA as a means of predicting a benefit from gefitinib (IRESSA) therapy in Japanese patients with non-small cell lung cancer (NSCLC). We obtained pairs of tumour and serum samples from 42 patients treated with gefitinib. EGFR mutation status was determined by a direct sequencing method and by Scorpion Amplification Refractory Mutation System (ARMS) technology. EGFR mutations were detected in the tumour samples of eight patients and in the serum samples of seven patients. EGFR mutation status in the tumours and serum samples was consistent in 39 (92.9%) of the 42 pairs. EGFR mutations were strong correlations between both EGFR mutation status in the tumour samples and serum samples and objective response to gefitinib (Po0.001). Median progression-free survival time was significantly longer in the patients with EGFR mutations than in the patients without EGFR mutations (194 vs 55 days, P ¼ 0.016, in tumour samples; 174 vs 58 days, P ¼ 0.044, in serum samples). The results suggest that it is feasible to use serum DNA to detect EGFR mutation, and that it's potential as a predictor of response to, and survival on gefitinib is worthy of further evaluation.

Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors

“…Kimura et al (2006Kimura et al ( , 2007 reported the ability to detect EGFR mutations in serum samples of patients with advanced NSCLC with approximately 75% sensitivity. More recently, Maheswaran et al (2008) reported 92% sensitivity in the detection of EGFR mutations in isolated circulating tumor cells, including the detection of the T790M-resistant mutants in patients undergoing TKI therapy.…”

Efficacy of gefitinib for non‐adenocarcinoma non‐small‐cell lung cancer patients harboring epidermal growth factor receptor mutations: A pooled analysis of published reports

“…(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) The study included any reports based on the method of DNA isolation from fresh tissue or paraffin-embedded tissue, and the technique used to enhance tumor-derived DNA, which included either microdissection or use of the more sensitive polymerase chain reaction (PCR) amplification techniques. Not all consecutive NSCLC patients were included in the EGFR mutation analysis in every study.…”

Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study

“…This can be extracted from plasma and serum, providing an opportunity to develop a less-invasive and more accessible source of tumour DNA for mutation detection. Previous studies have demonstrated the feasibility of detecting tumour-specific mutations in cfDNA from patients with cancer, including detection of epidermal growth factor receptor mutations in patients with non-small-cell lung cancer (Kimura et al, 2006(Kimura et al, , 2007 and KRAS mutations in patients with pancreatic and colorectal cancers (Sorenson, 2000). More recently, BRAF mutations have been detected in cfDNA of patients with melanoma (Daniotti et al, 2007;Shinozaki et al, 2007;Yancovitz et al, 2007).…”