Failure in Bevacizumab (Avastin) Early Stage Colon Cancer NSABP Trial May Not Be Absolute

Last month the news that Roche’s drug bevacizumab (Avastin) failed to improve disease-free survival in a trial of patients with early stage colon cancer made a big media splash. Norman Wolmark, MD, Allegheny General Hospital, Pittsburgh, Pennsylvania, addressed the study’s full results in a press conference the day before a scheduled plenary presentation at ASCO.

The NSABP Protocol C-08 trial was funded by the National Cancer Institute and enrolled 2710 patients from at least 245 treatment centers. Following tumor resection, patients with stage II or III colon cancer were randomized to receive 6 months of a modified FOLFOX6 chemotherapy regimen with or without bevacizumab. Patients in the combination arm continued with bevacizumab for 6 months after completion of chemotherapy. Patients were followed for a median of 3 years, with a primary endpoint of disease-free survival. Dr. Wolmark said the hope was that because bevacizumab prolongs survival in metastatic colon cancer, adding it to treatment for early stage colon cancer might affect cure, in some cases. The researchers’ goal never materialized, and the trial was panned as a failure.

“Nobody likes to fail,” Dr. Wolmark said. “Just how badly did we fail?” he asked. “Did we fail with distinction? Did we fail cum laude, with a hope of redemption?” He said that while the 3-year rate of survival was disappointing, with 77.4% of patients in the combination group arm disease-free at 35.6 months compared with a similar 75.5% in the chemotherapy group, a review of the first year’s results suggested that bevacizumab demonstrated significant efficacy early on.

“There’s no sense in trying to build up a false sense of drama and anticipation for these results,” acknowledged Dr. Wolmark. At the same time, he explained that the first year’s rates of disease-free survival favored bevacizumab so significantly that the trial came close to meeting the efficacy boundaries for stopping early. “We saw a robust benefit with bevacizumab,” Dr. Wolmark said, adding that the benefit diminished over time and eventually disappeared.

Dr. Wolmark and his colleagues consider the results promising enough to warrant additional investigation. “Clearly strong consideration should be given to clinical trials that use bevacizumab for periods of time well beyond the 1 year that was used in NSABP.” He said they hope to start a trial soon that will examine the use of bevacizumab for 2 years.