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FcγR and EGFR Polymorphisms as Predictive Markers of Cetuximab Efficacy in Metastatic Colorectal Cancer

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Abstract

Background and Objectives

Cetuximab shows activity in KRAS (Kirsten rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer (mCRC). Recent studies have demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in mCRC. We investigated the associations of FcγR (fragment C γ receptor) and EGFR (epidermal growth factor receptor) polymorphisms with the outcome of mCRC patients treated with cetuximab and FOLFIRI (folic acid/5-fluorouracil/irinotecan) as second-line therapy in the FLIER (Cetuximab Plus Folinic Acid/5-Fluorouracil/Irinotecan in KRAS Wild-Type Metastatic Colorectal Cancer as a Second-Line Treatment) study.

Methods

A total of 57 patients were evaluated in this study. The association of each polymorphism with the response rate, progression-free survival, and overall survival was analyzed.

Results

A tendency for longer overall survival was observed in patients with the EGFR CA repeat ≥36 genotype than in those with the ≤35 genotype (600 versus 483 days, P = 0.051). The haplotype containing the 131H and 158V alleles was associated with a lower response rate than the other haplotypes (P = 0.018). These results are contrary to previously published results.

Conclusion

Our data suggest that FcγR and EGFR CA repeat polymorphisms may be associated with the outcome of mCRC patients treated with cetuximab and FOLFIRI, although further investigations will be needed to confirm the association of FcγR and EGFR polymorphisms with the efficacy of cetuximab.

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Acknowledgments

This study was supported in part by a non-profit organization, the Epidemiological and Clinical Research Information Network (ECRIN), and by Japan Society for the Promotion of Science (JSPS) KAKENHI grant numbers 21591725 and 19591545. We thank Ms. Mai Hatta for her excellent clinical research coordination.

Disclosure Statement

The authors have no conflicts of interest that are directly relevant to the content of this article.

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Authors and Affiliations

  1. Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Yuka Inoue, Shoichi Hazama, Ryouichi Tsunedomi, Shigefumi Yoshino & Masaaki Oka

  2. Kansai Medical University Hirakata Hospital, Hirakata, 573-1191, Japan

    Shigeyoshi Iwamoto

  3. Nishinomiya Municipal Central Hospital, Nishinomiya, 663-8014, Japan

    Yasuhiro Miyake

  4. Osaka General Medical Center, Osaka, 558-8558, Japan

    Chu Matsuda

  5. Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, 755-8505, Japan

    Naoko Okayama, Yuji Hinoda, Takahiro Yamasaki & Yutaka Suehiro

  6. Tokai Central Hospital, Kakamigahara, 504-8601, Japan

    Junichi Sakamoto

  7. Cancer Center, Aichi Medical University, Nagakute, 480-1195, Japan

    Hideyuki Mishima

Authors
  1. Yuka Inoue
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  2. Shoichi Hazama
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  11. Shigefumi Yoshino
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Corresponding author

Correspondence to Shoichi Hazama.

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Inoue, Y., Hazama, S., Iwamoto, S. et al. FcγR and EGFR Polymorphisms as Predictive Markers of Cetuximab Efficacy in Metastatic Colorectal Cancer. Mol Diagn Ther 18, 541–548 (2014). https://doi.org/10.1007/s40291-014-0103-6

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  • DOI: https://doi.org/10.1007/s40291-014-0103-6

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