Navigating later lines of treatment for advanced colorectal cancer - optimizing targeted biological therapies to improve outcomes.

Abstract Colorectal cancer (CRC) is the third most commonly diagnosed cancer among males and second among females worldwide. The treatment landscape for advanced CRC (aCRC) is rapidly evolving and there are now a number of randomized trials assessing treatment of aCRC beyond first-line, prompting important questions about how to optimize therapy and maximize benefit. The availability of targeted agents has increased the complexity of post-progression treatment of aCRC. Targeted biological agents with varying modes of action are now approved for use in second-line and beyond, including the VEGF-inhibitors bevacizumab and aflibercept, the VEGFR/multikinase-inhibitor regorafenib, and the EGFR-inhibitors cetuximab and panitumumab. This article provides a systematic overview of the available phase III trial data, discusses biomarkers predictive of response to treatment, addresses safety concerns associated with specific agents, and provides practical, evidence-based recommendations for the later lines of treatment for patients with unresectable aCRC.