Sequencing of treatment in metastatic colorectal cancer: Where to fit the target

Colorectal cancer is a lethal disease if not discovered early. Even though appropriate screening and preventive strategies are in place in many countries, a significant number of patients are still diagnosed at late stages of the disease. The management of metastatic colorectal cancer remains a significant clinical challenge to oncologists worldwide. While cytotoxic regimens constitute the main treatment of choice in this patient population, addition of the five biologics (bevacizumab, cetuximab, aflibercept, panitumumab and regorafenib) to these regimens has improved clinical outcomes. The most commonly used cytotoxic regimens include doublet combinations (FOLFOX/XELOX or FOLFIRI). Many clinical trials have been published and others are underway to compare the biologic agents with one another in order to prove the superiority of one regimen over another. Metastatic colorectal cancer patients have many treatment options; however, the optimal use and sequence of targeted agents remain to be determined. This review entails concise and updated clinical data on the management of metastatic colorectal cancer. The aim of the review is to determine where to fit the five biologic targets into the treatment algorithm of metastatic colorectal cancer patients and to derive treatment sequences that would achieve best clinical outcome based on the current available data.