Regorafenib: from bench to bedside in colorectal cancer

Colorectal cancer (CRC) remains the third cause of cancer-related mortality in the USA. Despite the advances in screening, many patients present with incurable metastatic disease. Chemotherapy forms the basis of treatment for patients with advanced disease. Angiogenesis is an important step in developing metastases and, therefore, blocking the VEGF pathway seems promising. The development of bevacizumab as a monoclonal antibody targeting the VEGF pathway improved progression-free survival and overall survival in the metastatic settings, with no improvement in disease-free or overall survival in the adjuvant settings. Small molecules such as tyrosine-kinase inhibitors have been long evaluated in metastatic CRC with disappointing results in improving outcome. Most recently, the CORRECT study has resulted in improved outcome in patients with metastatic CRC who were heavily pretreated when they received regorafenib.