Use of a High-Throughput Genotyping Platform (OncoMap) for RAS Mutational Analysis to Predict Cetuximab Efficacy in Patients with Metastatic Colorectal Cancer

• Published in: Cancer research and treatment Vol. 49; no. 1; pp. 37 - 43
• Main Authors: Kim, Dalyong, Hong, Yong Sang, Kim, Jeong Eun, Kim, Kyu-pyo, Lee, Jae-Lyun, Chun, Sung-Min, Kim, Jihun, Jang, Se Jin, Kim, Tae Won
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01.01.2017; 대한암학회
• Subjects: Antineoplastic Agents, Immunological - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cetuximab - therapeutic use; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; DNA Mutational Analysis - methods; Drug Resistance, Neoplasm; Exons; Female; High-Throughput Nucleotide Sequencing; Humans; Kaplan-Meier Estimate; Middle Aged; Mutation; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Original; Prognosis; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Recurrence; Treatment Outcome; 의약학; RAS genes; Colorectal neoplasms; Cetuximab; High-throughput nucleotide sequencing
• ISSN: 1598-2998; 2005-9256
• DOI: 10.4143/crt.2016.069

Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the genes beyond exon 2. We performed extended Mutational analysis using a high-throughput genotyping platform (OncoMap) and evaluated extended analysis for predicting cetuximab efficacy in patients harboring wild-type exon 2 tumors following Sanger sequencing. Extended analysis was performed on 227 wild-type exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in and , and included exon 15. We assessed efficacy by the new mutation status. The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in exon 2 and 32 (14.1%) beyond exon 2. Survival differences were observed after dividing patients into the wild-type group (n=170) and mutant group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88). Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.