The development of bevacizumab in noncolorectal gastrointestinal malignancies: gastroesophageal, pancreatic, and hepatocellular carcinoma.

Bevacizumab (Avastin, Genentech) is a potent inhibitor of vascular endothelial growth factor A that has demonstrated modest antitumor activity across a broad range of malignancies when combined with chemotherapy. In colorectal cancer, bevacizumab in combination with chemotherapy is a standard of care for first-line therapy, and is used as second-line therapy in both bevacizumab-naive patients and those who have progressed on first-line therapy containing bevacizumab. Bevacizumab has been examined in nongastrointestinal malignancies as well. Across these multiple studies, virtually all of which demonstrate some improvement in progression-free survival, the combination of chemotherapy and bevacizumab has not led to a significant improvement in overall survival. Unfortunately, the addition of bevacizumab to chemotherapy translates into only slight improvement in overall survival in a few malignancies, including colorectal cancer. In this review, we highlight the development of bevacizumab in noncolorectal gastrointestinal malignancies, and potential future directions in antiangiogenic drug development.