FcγR and EGFR polymorphisms as predictive markers of cetuximab efficacy in metastatic colorectal cancer.
OBJECTIVE
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.


CONCLUSIONS
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.
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
Y
Inoue
Shoichi
S
Hazama
Shigeyoshi
S
Iwamoto
Yasuhiro
Y
Miyake
Chu
C
Matsuda
Ryouichi
R
Tsunedomi
Naoko
N
Okayama
Yuji
Y
Hinoda
Takahiro
T
Yamasaki
Yutaka
Y
Suehiro
Shigefumi
S
Yoshino
Junichi
J
Sakamoto
Hideyuki
H
Mishima
Masaaki
M
Oka
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D017452:Receptors, IgG; D000077150:Oxaliplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab