Genome-wide DNA Methylation Status is a Predictor of the Efficacy of Anti-EGFR Antibodies in the Second-line Treatment of Metastatic Colorectal Cancer: Translational Research of the EPIC Trial

Overview

Journal Int J Colorectal Dis

Specialties Gastroenterology
General Surgery

Date 2024 Jun 11

PMID 38862615

Authors

Kota Ouchi

Shin Takahashi

Keiju Sasaki

Yuya Yoshida

Sakura Taniguchi

Yuki Kasahara

Keigo Komine

Hiroo Imai

Ken Saijo

Hidekazu Shirota

Masanobu Takahashi

Chikashi Ishioka

Affiliations

Soon will be listed here.

Abstract

Purpose: The genome-wide DNA methylation status (GWMS) predicts of therapeutic response to anti-epidermal growth factor receptor (EGFR) antibodies in treating metastatic colorectal cancer. We verified the significance of GWMS as a predictive factor for the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer.

Methods: Clinical data were obtained from a prospective trial database, and a genome-wide DNA methylation analysis was performed. GWMS was classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). The patients were divided into subgroups according to the treatment arm (cetuximab plus irinotecan or irinotecan alone) and GWMS, and the clinical outcomes were compared between the subgroups.

Results: Of the 112 patients, 58 (51.8%) were in the cetuximab plus irinotecan arm, and 54 (48.2%) were in the irinotecan arm; 47 (42.0%) were in the HMCC, and 65 (58.0%) were in the LMCC group regarding GWMS. Compared with the LMCC group, the progression-free survival (PFS) was significantly shortened in the HMCC group in the cetuximab plus irinotecan arm (median 1.4 vs. 4.1 months, p = 0.001, hazard ratio = 2.56), whereas no significant differences were observed in the irinotecan arm. A multivariate analysis showed that GWMS was an independent predictor of PFS and overall survival (OS) in the cetuximab plus irinotecan arm (p = 0.002, p = 0.005, respectively), whereas GWMS did not contribute to either PFS or OS in the irinotecan arm.

Conclusions: GWMS was a predictive factor for the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer.

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