Given the data presented above, it would be unusual for patients to remain bevacizumab naïve at this time (21). Perhaps more clinically applicable is the use of regorafenib in the management of patients who have become refractory to all other therapeutic options, including bevacizumab (8). As we go forward, important questions will address how to individualize the selection of the various anti-angiogenic agents for inclusion Inhibitors,research,lifescience,medical or exclusion in the therapeutic management of metastatic

colorectal cancer. Thus far, increased patient age does not appear to increase adverse event rate associated with bevacizumab (14). This does not consider, however, whether the impact of these adverse events, when they do occur, result Inhibitors,research,lifescience,medical in an increased morbidity or mortality after a certain age. Regardless of age, another important consideration will be whether certain adverse events associated with the use of these agents preclude their repeated use. For instance, it is unclear whether a patient who has experienced a bowel perforation on bevacizumab in the first line setting (which Inhibitors,research,lifescience,medical is

currently the most likely scenario as it has been approved for nearly a decade) should preclude the use of other anti-angiogenic therapies in the future. Other ways to select for patients who are more likely to benefit when their cancers are treated with these anti-angiogenic agents may evolve from within their tumors’ biology. There may be a role for measuring or identifying different biomarkers that would indicate a higher expected benefit from these agents. Such information would further guide the decision to include these agents when weighed against the risk posed to that individual Inhibitors,research,lifescience,medical by the agents’ adverse event profile. As each of these agents’ effectiveness and tolerability in each line of therapy and in the context of the individual patient characteristics becomes clear as separate Inhibitors,research,lifescience,medical entities, it will be important to evaluate if

any of these agents are more effective and/or more tolerable than another in each setting, through trials that directly compare them to one another. Until the efficacy and tolerability of each of these agents is understood in each line of therapy and with each possible chemotherapeutic combination, employment of each agent should be limited to the indications that they are presently assigned, based upon the available enough benefit and tolerance data. Fortunately, while the remaining questions are being explored, there are a variety of different options for the use of anti-angiogenic treatment in all lines of therapy in metastatic colorectal cancer. Acknowledgements Disclosure: Dr Hwang is a consultant and speaker for Roche/Genentech, Bayer and Onyx; Dr Smaglo declare no conflict of interest.
Therapies targeting angiogenesis are an integral modality of modern anti-tumor treatment for a number of malignancies, in particular metastatic colorectal selleck kinase inhibitor cancer (CRC).