Northwestern Medicine recently joined a landmark clinical trial to investigate if a vaccine made from a patient’s own brain tumor is effective in slowing tumor progression and extending survival. The randomized phase 2 trial will study how well giving the study vaccine with or without Avastin (bevacizumab) works in treating patients with recurrent glioblastoma multiforme (GBM).
(Avastin, Genentech Inc.- Year approved:2009)
Avastin (or bevacizumab to the scientific community) is a humanised monoclonal antibody that is directed against all biologically active forms of VEGF. Antibodies are molecules that are typically a normal part of the human immune system. An antibody is meant to bind to a very specific target which is then typically destroyed and removed by the body. Avastin is an antibody that binds VEGF and acts to block its action.
Bevacizumab was one of the first antiangiogenic agents to demonstrate activity against metastatic kidney cancer. Bevacizumab is administered intravenously every two weeks. On July 31, 2009, the FDA granted approval for the use of Avastin in combination with interferon-? for the treatment of patients with metastatic renal cell carcinoma. The approval was based on results published in the journal Lancet in 2007. In this double-blind phase III trial 649 patients with metastatic kidney cancer who had undergone nephrectomy, were randomized to either bevacizumab plus Interferon-? or placebo plus Interferon-? as a first-line treatment. Median progression-free survival of patients was significantly improved in those receiving the combination treatment including Bevacizumab and Interferon-? compared to the control group (10.2 vs 5.4 months). Response rates were also significantly improved in the Bevacizumab and Interferon-? groups (31% vs 13%). The most common severe (grade 3) toxicity was fatigue: 12% in the bevacizumab and IFN arm versus 8% in the control arm.
A second multicenter phase III trial which was performed in 2008 and which was conducted in the United States and Canada, was nearly identical in design with the exception that it lacked a placebo element and did not require prior nephrectomy. In this second study, the average progression-free survival was 8.5 months in patients receiving The combination of Bevacizumab and Interferon-? compared to 5.2 months for patients receiving Interferon-? therapy alone. The overall response rate was in favour of the combination group (25.5% vs 13.1%). However, both studies failed to show any significant difference regarding overall survival between the combination of Bevacizumab and Interferon-? versus Interferon-? alone (18.3 vs 17.4 months).
Bevacizumab (trade name Avastin, Genentech/Roche) is an angiogenesis inhibitor, a drug that slows the growth of new blood vessels. It is licensed to treat various cancers, including colorectal, lung, breast (outside the USA), glioblastoma (USA only), kidney and ovarian.
Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A). VEGF-A is a chemical signal that stimulates angiogenesis in a variety of diseases, especially in cancer. Bevacizumab was the first clinically availableangiogenesis inhibitor in the United States.
Bevacizumab was approved by the U.S. Food and Drug Administration (FDA) for certainmetastatic cancers. It received its first approval in 2004, for combination use with standardchemotherapy for metastatic colon cancer.It has since been approved for use in certain lung cancers, renal cancers, and glioblastoma multiforme of the brain.
At one point bevacizumab was approved for breast cancer by the FDA, but the approval was revoked on 18 November 2011. The approval for breast cancer was revoked because, although there was evidence that it slowed progression of metastatic breast cancer, there was no evidence that it extended life or improved quality of life, and it caused adverse effects including severe high blood pressure and hemorrhaging. In 2008, the FDA gave bevacizumab provisional approval for metastatic breast cancer, subject to further studies. The FDA’s advisory panel had recommended against approval. In July 2010, after new studies failed to show a significant benefit, the FDA’s advisory panel recommended against the indication for advanced breast cancer. Genentech requested a hearing, which was granted in June 2011. The FDA ruled to withdraw the breast cancer indication in November 2011. FDA approval is required for Genentech to market a drug for that indication. Doctors may sometimes prescribe it for that indication, although insurance companies are less likely to pay for it. The drug remains approved for breast cancer use in other countries including Australia.
Clinical trials are underway for many other indications including ovarian cancer, pediatric osteosarcoma, and certain non-malignant eye diseases. In the curative setting (adjuvant therapy), clinical studies are underway in breast cancer and lung cancer.