Molecular Predictors of Combination Targeted Therapies (Cetuximab, Bevacizumab) in Irinotecan-Refractory Colorectal Cancer (BOND-2 Study)

作者：Zhang Wu; Azuma Mizutomo; Lurje Georg; Gordon Michael A; Yang Dongyun; Pohl Alexandra; Ning Yan; Bohanes Pierre; Gerger Armin; Winder Thomas; Hollywood Ellen; Danenberg Kathleen D; Saltz Leonard; Lenz Heinz Josef^*

来源：Anticancer Research, 2010, 30(10): 4209-4217.

• Metastatic colorectal cancer
• gene expression level
• polymorphisms
• clinical outcome
• cetuximab
• bevacizumab
• irinotecan

Background: To test whether intratumoral gene expression levels and germline polymorphisms predict clinical outcome in metastatic colorectal cancer (mCRC) patients treated with cetuximab and bevacizumab plus irinotecan (CBI) vs. cetuximab and bevacizumab (CB)(BOND2). Patients and Methods: Genomic DNA was extracted for genotyping from 65 patients (31: CBI arm and 34: CB arm). Thirty five patients had tissue samples available for the gene expression assay (18: CBI arm and 17: CB arm). Results: High intratumoral gene expression levels of EGFR, VEGFR2 and NRP1 were associated with longer overall survival (OS) in patients receiving combined monoclonal antibodies with or without irinotecan. FCGR3A V158F, CyclinD1 A870G and EGFR R497K polymorphisms are associated with clinical outcome in patients received combined cetuximab and bevacizumab. Conclusions: Intratumoral gene expression levels of EGER, VEGFR2 and NRP as well as polymorphisms in FCGR3A, CyclinD1 and EGER could predict clinical outcome in mCRC patients enrolled in BOND2, independent of KRAS mutation status.

• 出版日期2010-10