Role of KRAS and EGFR As Biomarkers of Response to Erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21

• DOI: 10.1200/jco.2007.14.8924
• Publication Date: 2008-07-15T01:09:36Z
• Authors: Chang-Qi Zhu; Gilda da Cunha Sa...; Keyue Ding; Akira Sakurada; Jean-Claude Cutz; Ni Liu; Tong Zhang; Paula Marrano; Marlo Whitehead; Jeremy A. Squire; Suzanne Kamel-Reid; Lesley Seymour; Frances A. Shepherd; Ming-Sound Tsao
• Keywords: EGFR Inhibitors; Erlotinib Hydrochloride

To evaluate the effect of KRAS and epidermal growth factor receptor (EGFR) genotype on response to erlotinib treatment in BR.21, placebo-controlled trial.We analyzed 206 tumors for mutation, 204 EGFR 159 gene copy by fluorescent situ hybridization (FISH). We reanalyzed deletion/mutation using two highly sensitive techniques that detect abnormalities samples with 5% 10% tumor cellularity. mutation was direct sequencing.Thirty patients (15%) had mutations, 34 (17%) exon 19 deletion or 21 L858R 61 (38%) high (FISH positive). Response rates were wild-type mutant (P = .69), 7% 27% .03), FISH-negative 21% FISH-positive .02). Significant survival benefit from therapy observed (hazard ratio [HR] 0.69, P .03) FISH positivity (HR 0.43, .004) but not 1.67, .31), 0.74, .09), 0.55, .12), negativity 0.80, .35). In multivariate analysis, only status prognostic poorer .025) predictive differential .005).EGFR mutations number are erlotinib. is strongest marker a significant