Systemic treatment for metastatic colorectal cancer

Abstract

Significant progress has been achieved in the treatment of metastatic colorectal cancer (mCRC) patients during the last 20 years. There are currently numerous treatments available for the first-line treatment of mCRC. Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC. The development of next-generation sequencing and whole-exome sequencing, which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment, has resulted in tremendous breakthroughs in DNA sequencing technology in recent years. The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage, presence of high-risk pathologic characteristics, microsatellite instability status, patient age, and performance status. Chemotherapy, targeted therapy, and immunotherapy are the main systemic treatments for patients with mCRC. Despite the fact that these novel treatment choices have increased overall survival for mCRC, survival remains optimal for individuals with non-metastatic disease. The molecular technologies currently being used to support our ability to practice personalized medicine; the practical aspects of applying molecular biomarkers to regular clinical practice; and the evolution of chemotherapy, targeted therapy, and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.

Keywords: Systemic treatment; Metastatic colorectal cancer; Personalized medicine; Biomarkers; Chemotherapy; Targeted therapy; Immunotherapy

Core Tip: Advances in the molecular profiling of metastatic colorectal cancer allow treatment to be tailored to the biologic characteristics of the tumor for certain patient subgroups. Although cures are still rare, more people can expect to live longer. Genomic profiling enables therapy selection, allowing more individuals to benefit while exposing fewer to the harm of ineffective medicines. An important component in determining treatment results is the choice of an effective first-line therapy, which should consider both clinical considerations and molecular indicators. The systemic treatments used in the first-line regimen determine the second-line regimen. Third-line therapy, which includes epithelial growth factor receptor inhibitors for patients with rat sarcoma virus wild-type, should consider molecular profiling. Patients with high microsatellite instability illnesses may be candidates for immunotherapy with pembrolizumab or nivolumab plus ipilimumab.