Association of CpG island methylator phenotype (CIMP) with inferior progression-free survival with anti-EGFR monoclonal antibody therapy in metastatic colorectal cancer.

3633 Background: Deranged epigenetic regulation is thought to play an important role in pathogenesis and behavior of metastatic colorectal cancer (mCRC). The CpG island methylator phenotype (CIMP) is associated with distinct tumor biology, which may have differential sensitivity to targeted drug therapy. We hypothesized that methylation status affects susceptibility to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs). Methods: 195 mCRC patients initially tested as KRAS wild-type had tumor tissue successfully tested for CIMP status via bisulfite pyrosequencing and PCR amplification of MINT1, MINT2, and MINT31 loci and promoter sequences of p14, p16, and hMLH1. Next generation sequencing for KRAS, BRAF, and NRAS mutations was done. The duration of the first anti-EGFR mAb treatment and reason for cessation was retrospectively determined, and log-rank test was used for comparisons of progression-free survival (PFS). Cox regression analysis was performed. Results: 162 patients received...