Although adding Avastin® (bevacizumab) to FOLFOX chemotherapy showed an effect on reducing recurrences in people with stage II and III colon cancer one year after treatment began, the impact began to fade in the second year, and was completely gone at three years.
There was a transient benefit in the year during which Avastin was given every two weeks, with a 40 percent reduction in the risk of recurrence. At the end of the first year patients who had been given Avastin had a 94.2 percent chance of being alive and cancer-free compared to 90.7 percent of patients who did get it.
However, at three years disease-free survival was 77.4 percent in the Avastin patients compared to 75.5 percent for those without it, a non-significant difference.
The C-08 clinical trial randomly assigned 2,710 patients with stage II or stage III to either FOLFOX or FOLFOX plus Avastin for six months. In addition, patients in the Avastin arm received an additional six months of Avastin.
The study found no differences between stage II or stage III disease in the effect that adding Avastin had. About 25 percent of patients had stage II disease.
Speaking for the National Surgical Adjuvant Breast and Bowel Project (NSABP), Dr. Norman Wolmark concluded,
The addition of bevacizumab to modified FOLFOX did not result in an overall statistically significant prolongation in disease-free survival. There was a transient benefit in DFS during the one-year interval that bevacizumab was utilized. Consideration may be given to clinical trials assessing longer duration of bevacizumab administration.
Dr. Lee Ellis of M.D. Anderson Cancer Center, in discussing the results of the C-08 trial during the ASCO Plenary Session, raised concerns about future clinical trials of Avastin for stage II and III colon cancer.
- How long does Avastin need to be given to maintain its benefit?
- Is the real improvement in disease-free survival about 3 to 5 percent?
- Does this benefit justify the inconvenience to patients of regular IV infusions, cost, and potential side effects?
- Could long-term anti-VEGF therapy have an adverse effect on the central nervous system?
He pointed out that for some patients receiving Avastin in the C-08 trial there was pain, depression, and dizziness serious enough to interfere with activities of daily living, as well as increased high blood pressure. He urged long-term followup of patients who receive long-term adjuvant treatment with anti-VEGF agents like Avastin including cognitive testing, and tests of both the central nervous and cardiovascular systems.