Current Treatment Landscape for Third- or Later-Line Therapy in Metastatic Colorectal Cancer

Purpose of Review The aim of this paper is to summarize the current treatment landscape in metastatic colorectal cancer, as well as those on the horizon in the third-line and beyond settings. Recent Findings Herein, recent data regarding TAS-102, regorafenib, and novel anti-angiogenic agents are described. Data on chemotherapy re-challenge and EGFR re-challenge is reviewed. A summary of data on the use of BRAF-targeted therapies, HER-2-targeted therapies, rare fusions (NTRK, RET), MET amplification, and KRAS G12C is included, as well as a brief review on the current role of immune checkpoint inhibitors in metastatic colorectal cancer. Multiple new agents are on the horizon. There is increasing relevance of next generation sequencing to look for rare targets, and potentially to assess tumor mutational burden. ctDNA appears to be a valuable asset which may guide the use of therapies in the re-challenge setting.