Bevacizumab is a recombinant humanized monoclonal antibody that targets all forms of VEGF-A. This antibody binds to and prevents VEGF-A from interacting with the target VEGF receptors. Bevacizumab can be safely and effectively combined with 5-FU-, irinotecan-, and oxaliplatin-based chemotherapy in the treatment of metastatic colorectal cancer. Bevacizumab is FDA approved as a first-line treatment for metastatic colorectal cancer in combination with any intravenous fluoropyrimidinecontaining regimen and is now also approved in combination with chemotherapy for metastatic NSCLC and breast cancer. One potential advantage of this antibody is that it does not appear to exacerbate the toxicities typically observed with cytotoxic chemotherapy. The main safety concerns associated with bevacizumab include hypertension, an increased incidence of arterial thromboembolic events (transient ischemic attack, stroke, angina, and myocardial infarction), wound healing complications, gastrointestinal perforations, and proteinuria.
Ziv-aflibercept is a recombinant fusion protein made up of portions of the extracellular domains of human VEGF receptors (VEGFR) 1 and 2 fused to the Fc portion of the human IgG1 molecule. This molecule serves as a soluble receptor to VEGFA, VEGF-B, and placental growth factor (PlGF), and it binds with significantly higher affinity to VEGF-A than bevacizumab. Presumably, binding of the VEGF ligands prevents their subsequent interactions with the target VEGF receptors, which then results in inhibition of downstream VEGFR signaling. This agent is FDA-approved in combination with the FOLFIRI regimen for patients with metastatic colorectal cancer that has progressed on oxaliplatin-based chemotherapy. The main adverse effects are similar to what has been observed with bevacizumab.
Ramucirumab is an IgG1 antibody that targets the VEGFR2 receptor. This agent inhibits binding of the VEGF ligands, VEGF-A, VEGF-C, and VEGF-D, to the target VEGF-R2 receptor, which then results in inhibition of downstream VEGFR signaling. This agent is now FDA-approved for advanced gastric or gastroesophageal junction adenocarcinoma, metastatic NSCLC, and metastatic CRC. The main adverse events are similar to those observed with bevacizumab and other anti-VEGF inhibitors.
Sorafenib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), especially VEGF-R2 and VEGF-R3, platelet-derived growth factor-β (PDGFR-β), and raf kinase. It was initially approved for advanced renal cell cancer and is also approved for advanced hepatocellular cancer.
Sunitinib is similar to sorafenib in that it inhibits multiple RTKs, although the specific types are somewhat different. They include PDGFR-α and PDGFR-β, VEGF-R1, VEGF-R2, VEGFR3, and c-kit. It is approved for the treatment of advanced renal cell cancer and for the treatment of gastrointestinal stromal tumors after disease progression on or with intolerance to imatinib.
Pazopanib is a small molecule that inhibits multiple RTKs, especially VEGF-R2 and VEGF-R3, PDGFR-β, and raf kinase. This oral agent is approved for the treatment of advanced renal cell cancer.