Association between polymorphisms in EGFR and tumor response during cetuximab and oxaliplatin-based combination therapy in metastatic colorectal cancer: Analysis of data from two clinical trials.

Abstract

Predicting tumor response prior to starting anti-epidermal growth factor receptor (EGFR) antibody therapy would benefit patients with advanced/metastatic colorectal cancer (mCRC). The present study investigated the association between efficacy of cetuximab treatment and gene polymorphisms of fragment C γ receptor (FcγR) 2A, FcγR3A and EGFR in patients with extended RAS/BRAF wild-type mCRC. Clinical data and specimens were obtained from 90 patients who participated in either of two clinical studies evaluating the first-line, cetuximab plus oxaliplatin-based treatment. It was hypothesized that polymorphisms H/H of FcγR2A, V/V of FcγR3A, K/K of EGFR and <36 CA repeats in the EGFR gene may be associated with a favorable tumor response. Multivariate analysis demonstrated that patients with the H/H polymorphism tended to have an improved tumor response compared with the non-H/H population, although the result was not significant [odds ratio, 2.25; 95% confidence interval (CI), 0.89–5.66; P=0.09]. Univariate analysis revealed increased tumor shrinkage in patients with the K/K polymorphism of EGFR compared with the other polymorphisms (mean ± standard deviation, −55.3±28.4 vs. −39.6±40.8%; P=0.04). Subsequent multivariate analysis confirmed that the K/K polymorphism of EGFR predicted greater tumor shrinkage (multiple linear regression analysis estimate, −19.3; 95% CI, −35.5 to 3.0; P=0.02), with the tendency toward a preferable response in patients with <36 CA EGFR gene repeats (estimate, −16.9; 95% CI; −34.4 to 0.6; P=0.06). However, other polymorphisms and clinical variables did not predict tumor shrinkage. In conclusion, the present study demonstrated that polymorphisms of EGFR, FcγR2A and FcγR3A may differentiate the patients that obtain the maximum benefit from cetuximab treatment.