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Medline ® Abstract for Reference 60

of 'Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations'

Correlation between gene expression of IGF-1R pathway markers and cetuximab benefit in metastatic colorectal cancer.
Huang F, Xu LA, Khambata-Ford S
Clin Cancer Res. 2012;18(4):1156. Epub 2012 Jan 31.
PURPOSE: This study examined potential correlations between markers related to the insulin-like growth factor-1 receptor (IGF-1R) pathway and clinical benefit from the anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in metastatic colorectal cancer (mCRC).
EXPERIMENTAL DESIGN: Gene expression profiles for 70 pretreatment specimens from metastatic lesions of patients with chemorefractory mCRC receiving cetuximab monotherapy were analyzed using 74 predefined Gene-Chip probesets representing 33 unique IGF-1R pathway markers to determine correlations with progression-free survival (PFS) and disease control rate.
RESULTS: Higher IGF-1R, higher GRB(7), and lower INSIG(2) expression were associated with longer PFS with cetuximab in univariate analyses, particularly in patients with wild-type K-Ras tumors: median, 122 versus 60 days (P = 0.01), 122 versus 57 days (P = 0.011), and 57 versus 156 days (P<0.0001), favoring higher IGF-1R, higher GRB(7), and lower INSIG(2) expression, respectively. Lower IGF-1 expression was associated with a PFS benefit with cetuximab,whereas lower IGFBP(3) and INSR expression levels showed trends for a PFS benefit. Lower INSIG(2) expression (vs. higher expression) was associated with greater PFS in the high epiregulin-expressing group (P = 0.001), but not in the low-expressing cohort suggesting an effect independent from the previously reported effect of epiregulin expression. Lower INSIG(2) expression was also associated with higher disease control rate in the overall population (51.4% vs. 11.4%; P = 0.001) and wild-type K-Ras subset (76.2% vs. 18.2%; P<0.0001).
CONCLUSIONS: These results suggest that markers of the IGF-1R pathway may play a role in predicting benefit from cetuximab therapy in mCRC. Additional clinical studies are warranted to validate these findings.
Bristol-Myers Squibb Co., Route 206 and Province Line Rd., Room E1.293, Princeton, NJ 08453, USA. fei.huang@bms.com