Genetic polymorphisms of FcγRIIa and FcγRIIIa are not predictive of clinical outcomes after cetuximab plus irinotecan chemotherapy in patients with metastatic colorectal cancer.
OBJECTIVE
The anti-epidermal growth factor receptor monoclonal antibody cetuximab has been shown to be effective in patients with wild-type KRAS metastatic colorectal cancer (mCRC). Fragment C γ receptor (FcγR) polymorphisms may predict the effectiveness of cetuximab, but this has not been established. This study investigated the clinical relevance of FcγR gene polymorphisms and KRAS status in iri-notecan-refractory mCRC patients treated with cetuximab.


METHODS
The total number of irinotecan-refractory mCRC patients studied was 118. Among them, 117 and 107 patients were screened for KRAS mutations and genetic polymorphisms of FcγRIIa-131H/R and FcγRIIIa-158V/F, respectively. The association of FcγR polymorphisms and KRAS mutations with clinical outcome was analyzed.


RESULTS
KRAS mutations were found in 33 patients (27.1%). Wild-type KRAS was associated with a better response rate (p < 0.001), longer progression-free survival (p < 0.001) and longer overall survival (p < 0.001). FcγRIIa H/H, H/R and R/R polymorphisms were observed in 54, 49 and 4 patients, respectively, and FcγRIIIa V/V, V/F and F/F polymorphisms were observed in 6, 65, and 36 patients, respectively. Clinical outcomes were not significantly associated with either FcγRIIa or FcγRIIIa polymorphisms or with combinations of KRAS status and FcγR polymorphisms.


CONCLUSIONS
The FcγRIIa and FcγRIIIa polymorphisms may not be useful molecular biomarkers for the activity of cetuximab in patients with mCRC.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Seong Joon
SJ
Park
Yong Sang
YS
Hong
Jae-Lyun
JL
Lee
Min-Hee
MH
Ryu
Heung Moon
HM
Chang
Kyu-pyo
KP
Kim
Yong Chel
YC
Ahn
Young-Soon
YS
Na
Dong-Hoon
DH
Jin
Chang Sik
CS
Yu
Jin Cheon
JC
Kim
Yoon-Koo
YK
Kang
Tae Won
TW
Kim
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D017452:Receptors, IgG / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin