Feb 08, 2012
Bevacizumab (Avastin) and Ovarian Cancer
By: Annekathryn Goodman, MD
February 4, 2012
The standard of care in the treatment of ovarian cancer combined aggressive surgical resection of cancer with combination chemotherapy using paclitaxel and carboplatin. Despite an 80 percent remission rate using this approach, over time, the majority of women with advanced ovarian cancer will experience recurrence of their cancer and ultimately will die from their cancer. There have been many trials to try and improve the survival for women with ovarian cancer.
It is important in interpreting studies to understand 2 terms that are used in publications. Progression free survival (PFS) means the interval of time when no cancer is detected on exam, labs, or xrays. PFS is the term now used for the older concept of being in remission from a cancer. Overall survival (OS) means the length of a person’s life from cancer diagnosis until death.
The most recently intensively studied agent is avastin (bevacizumab). Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF). VEGF is involved with the development of new, cancer induced blood vessels (which is called angiogenesis) that feed the cancer and are thought to be instrumental in the spread of these cancers. The general anticancer designation for this type of therapeutic agents is anti-angiogenesis factors.
The first studies of bevacizumab in women with ovarian cancer looked at bevacizumab by itself in recurrent cancer. These phase II trials showed that 16% to 21% tumors shrank and this effect lasted 6 months in up to 41% of women. The addition of bevacizumab to gemcitabine and carboplatin was recently reported to prolong progression free survival (PFS) in women with recurrent ovarian cancer.
The side effects and dangers of bevacizumab were first noted in these early studies. Side effects included hypertension, protein in the urine, bleeding from the lungs, and perforation of the intestine. In general patients did not have nausea, hair loss, and bone marrow suppression which is so common with conventional chemotherapy. The association of life threatening intestinal perforation was highly associated with the condition of partial and complete intestinal obstruction. Since these studies, oncologists have avoided the use of bevacizumab when women with ovarian cancer intestinal involvement by the cancer.
The Gynecologic Oncology Group reported their data on a large phase 3 study (GOG 218) with bevacizumab and carboplatin and taxol in 2010. Women who received bevacizumab combined with their chemotherapy and then 12 months of maintenance bevacizumab had an average of 3.8 more months before their cancers recurred. It is not clear whether the modest increase in PFS translates into a longer overall survival.
Bevacizumab is extraordinarily expensive with costs of $100,000 dollars per year for one patient treated. How do we put this all together? Many of the gains from cancer therapy are by stretching the envelope of survival a few months at a time. So the biggest question for bevacizumab is do the gains in progression free survival translate into overall survival? Currently the data on OS for these studies is not mature.