Here we see the NCCN guideline recommendations for patients with advanced or metastatic disease who would not be appropriate candidates for intensive therapy. Single-agent 5-FU/LV or capecitabine therapy is recommended with or without bevacizumab. Another option for patients with left-sided tumors containing wild-type RAS and BRAF genes is single-agent treatment with cetuximab or panitumumab. The PD-1 inhibitors, nivolumab or pembrolizumab, may be considered for patients with deficient mismatch repair proteins/high microsatellite instability. In addition, the combination of nivolumab and ipilimumab (a CTLA-4 inhibitor) may be considered in this same group of patients.