Initial Systemic Chemotherapy for Metastatic Colorectal Cancer

Selection of initial chemotherapy for metastatic colorectal cancer requires initial molecular profiling and an understanding of treatment goals. Substantial flexibility exists to tailor therapies to patient preferences and characteristics, including chemotherapy backbones of fluoropyrimidines, irinotecan, and/or oxaliplatin. Targeted therapy and immunotherapy can be utilized for molecular subsets, including recommendation to have patients with microsatellite unstable tumors proceed directly to immunotherapy. Antiangiogenic therapy, predominantly with the addition of bevacizumab, is commonly incorporated into cytotoxic chemotherapy strategies. Epidermal growth factor receptor inhibition is limited to patients with left-sided primary tumors without BRAF, KRAS, or NRAS mutations, and may improve outcomes for this subset when utilized as part of initial systemic chemotherapy. The toxicities of these regimens and duration of therapy should be incorporated into decisions about potential surgical resection in a multidisciplinary manner.