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

Br J Cancer. 2021 Sep;125(6):816-825. doi: 10.1038/s41416-021-01470-2. Epub 2021 Jun 29.

Abstract

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.

Publication types

  • Clinical Study
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cetuximab / administration & dosage*
  • Cetuximab / pharmacology
  • Colon / drug effects
  • Colon / pathology*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Databases, Genetic
  • Epigenomics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Neoplasm Metastasis
  • Panitumumab / administration & dosage*
  • Panitumumab / pharmacology
  • Rectum / drug effects
  • Rectum / pathology*
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Panitumumab
  • Cetuximab