Evaluation of CpG Island Methylator Phenotype as a Biomarker in Colorectal Cancer Treated With Adjuvant Oxaliplatin

CpG island methylator phenotype (CIMP) status was explored as a potential biomarker in 293 tumor specimens from patients with stage II or III in the Hellenic Cooperative Oncology Group HE6C/05 trial receiving either modified FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) or XELOX (capecitabine, oxaliplatin) adjuvant chemotherapy. Of the 293 specimens, 28 (9.6%) were CIMP+; however, no association with disease-free or overall survival was noted. In the present exploratory analysis, CIMP did not appear to be a prognostic biomarker in oxaliplatin-treated patients with resected colorectal cancer. Background: The CpG island methylator phenotype (CIMP) is a promising biomarker for irinotecan/5-fluorouracil/leucovorin chemotherapy for stage III colon cancer. In the present study, we evaluated whether CIMP is a prognostic biomarker for standard-of-care oxaliplatin-based adjuvant therapy. Materials and Methods: The HE6C/05 trial randomized 441 patients with stage II-III colorectal adenocarcinoma to adjuvant XELOX (capecitabine, oxaliplatin) or modified FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin). The primary and secondary objectives were disease-free and overall survival, respectively. CIMP status was determined using the DNA methylation status of CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1. Cox models were used to assess the association of CIMP with survival. Results: Of the 293 available tumors, 28 (9.6%) were CIMP+. On univariate Cox regression analysis, no significant differences in survival were observed between individuals with CIMP+ versus CIMP- tumors. CIMP+ tumors were more likely to be right-sided and BRAF mutant (chi(2), P < .001). In the multivariate model, TNM stage II (vs. stage III) was associated with a reduced risk of relapse (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.11-0.55; Wald's P < .001), and a colon primary located on the left side and earlier TNM stage were associated with a reduced risk of death (HR, 0.48; 95% CI, 0.28-0.81; P = .006; and HR, 0.22; 95% CI, 0.10-0.49; P < .001, respectively). Conclusion: In the present exploratory analysis, CIMP did not appear to be a prognostic biomarker in oxaliplatin-treated patients with resected colorectal cancer.