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. CONCLUSION: The FcγRIIa and FcγRIIIa polymorphisms may not be useful molecular biomarkers for the activity of cetuximab in patients with mCRC.
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. CONCLUSION: The FcγRIIa and FcγRIIIa polymorphisms may not be useful molecular biomarkers for the activity of cetuximab in patients with mCRC.
Authors: Su Jin Lee; Jongtae Lee; Jeeyun Lee; Se Hoon Park; Joon Oh Park; Young Suk Park; Ho Yeong Lim; Kyoung-Mee Kim; In-Gu Do; Sin-Ho Jung; Dong-Seok Yim; Won Ki Kang Journal: Invest New Drugs Date: 2013-09-07 Impact factor: 3.850
Authors: Janne B Kjersem; Eva Skovlund; Tone Ikdahl; Tormod Guren; Christian Kersten; Astrid M Dalsgaard; Mette K Yilmaz; Tone Fokstuen; Kjell M Tveit; Elin H Kure Journal: BMC Cancer Date: 2014-05-19 Impact factor: 4.430
Authors: E K Morgen; H-J Lenz; D J Jonker; D Tu; G Milano; F Graziano; J Zalcberg; C S Karapetis; A Dobrovic; C J O'Callaghan; G Liu Journal: Pharmacogenomics J Date: 2016-11-29 Impact factor: 3.245