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

Maeda,Hiromichi; Hazama,Shoichi; Iwamoto,Shigeyoshi; Oba,Koji; Tsunedomi,Ryouichi; Okayama,Naoko; Suehiro,Yutaka; Yamasaki,Takahiro; Nakagami,Yuki; Suzuki,Nobuaki; Nagano,Hiroaki; Sakamoto,Junichi; Mishima,Hideyuki; Nagata,Naoki

doi:10.3892/ol.2019.10787

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

Authors:
- Hiromichi Maeda
- Shoichi Hazama
- Shigeyoshi Iwamoto
- Koji Oba
- Ryouichi Tsunedomi
- Naoko Okayama
- Yutaka Suehiro
- Takahiro Yamasaki
- Yuki Nakagami
- Nobuaki Suzuki
- Hiroaki Nagano
- Junichi Sakamoto
- Hideyuki Mishima
- Naoki Nagata
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Affiliations: Cancer Treatment Center, Kochi Medical School Hospital, Kochi University, Nankoku, Kochi 783‑8505, Japan, Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Cancer Center, Aichi Medical University, Nagakute, Aichi 480‑1195, Japan, Department of Biostatistics, Graduate School of Medicine, University of Tokyo, Bunkyo, Tokyo 113‑0033, Japan, Division of Laboratory, Yamaguchi University Hospital, Ube, Yamaguchi 755‑8505, Japan, Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Tokai Central Hospital, Kakamigahara, Gifu 504‑8601, Japan, Kitakyushu General Hospital, Kitakyushu, Fukuoka 802‑8517, Japan
Published online on: August 29, 2019 https://doi.org/10.3892/ol.2019.10787
Pages: 4555-4562
Copyright: © Maeda et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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