Evaluation of the CpG island methylator phenotype as a predictive biomarker for adjuvant oxaliplatin-based chemotherapy in colorectal cancer.

592 Background: The CpG island methylator phenotype (CIMP) has previously been shown to be a predictive biomarker for 5-fluorouracil (5-FU)/leucovorin (LV)/irinotecan (IFL) adjuvant chemotherapy in stage III colon cancer patients. It is unknown if CIMP serves as a biomarker for standard-of-care oxaliplatin-based adjuvant therapy. Methods: HE6C05 randomized 441 patients with stage II/III colorectal adenocarcinoma to adjuvant oxaliplatin with either capecitabine (XELOX) or 5-FU/LV (mFOLFOX6) between November 2005 and January 2008. The primary objective was disease-free survival (DFS); overall survival (OS) was a secondary objective. The study closed early due to poor accrual with last follow-up in November 2013. Isolated DNA from 293 tumor samples was used to determine CIMP status based on methylation patterns at the CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1 loci. Cox univariate and multivariate models were used to assess the effects of CIMP on DFS and OS, accounting for interactions with TNM stage; site (ri...