Aflibercept, a new way to target angiogenesis in the second line treatment of metastatic colorectal cancer (mCRC)

Colorectal cancer (CRC) is a leading tumour worldwide, and the median survival of metastatic patients with the latest therapeutic options today reaches 30 months. Therefore, it is important to plan a therapeutic strategy, able to optimize the use of the available drugs (fluoropyrimides, oxaliplatin, irinotecan and target biologic therapy), with the objective of maximizing the long-term efficacy, reducing toxicities and assuring better quality of life for the patients with mCRC. Among the most recently available drugs for the treatment of mCRC, aflibercept, a new antiangiogenetic agent, should be considered a promising therapeutical option for the second line setting. In this review, the mechanism of action and preclinical evidence, as well as pharmacological and clinical aspects of aflibercept will be analysed. In particular, this drug has a peculiar and unique mechanism of action, inhibiting VEGF-A, -B and PlGF pathways, which may help to overcome tumour escape mechanisms to bevacizumab treatment. From a clinical point of view, the addition of aflibercept to FOLFIRI regimen was able to significantly improve all the clinical outcome with respect to the chemotherapy alone in second line treatment of mCRC patients, regardless of age, RAS status, and prior use of bevacizumab. Finally, the safety profile of aflibercept is well known and manageable in most of the patients. Aflibercept can be considered a novel standard of care in the second line setting and an important therapeutic option for mCRC patients.