The efficacy of anti-EGFR therapy in treating metastatic colorectal cancer differs between the middle/low rectum and the left-sided colon

• Published in: British journal of cancer 2021-09, Vol.125 (6), p.816-825
• Main Authors: Lee, Kun-Han, Chen, Wei-Shone, Jiang, Jeng-Kai, Yang, Shung-Haur, Wang, Huann-Sheng, Chang, Shih-Ching, Lan, Yuan-Tzu, Lin, Chun-Chi, Lin, Hung-Hsin, Huang, Sheng-Chieh, Cheng, Hou-Hsuan, Chao, Yee, Teng, Hao-Wei
• Format: Article
• Language: English
• Subjects: 631/67/1504/1885; 631/67/1857; 692/4028/67/1504/1885; 692/699/1503/1504/1885; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cetuximab - administration & dosage; Cetuximab - pharmacology; Colon - drug effects; Colon - pathology; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Databases, Genetic; Drug Resistance; Epidemiology; Epidermal growth factor; Epidermal growth factor receptors; Epigenomics; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Genetic analysis; Humans; Male; Metastases; Metastasis; Molecular Medicine; Neoplasm Metastasis; Oncology; Panitumumab - administration & dosage; Panitumumab - pharmacology; Patients; Rectum; Rectum - drug effects; Rectum - pathology; Retrospective Studies; Survival; Survival Analysis; Treatment Outcome; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-021-01470-2

Background Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers. Methods This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap. Results On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer. Conclusions Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.