HOLLYWOOD, FLA. — Adding the biologic agent bevacizumab to a standard chemotherapy regimen led to improved survival in a controlled study with nearly 600 previously treated patients with advanced colorectal cancer, according to a report at a symposium on gastrointestinal cancers sponsored by the American Society for Clinical Oncology.
This is the first time that patients with advanced colorectal cancer have received both bevacizumab, a humanized monoclonal antibody that binds to and inhibits vascular endothelial growth factor, and the chemotherapy combination known as FOLFOX4, which is oxaliplatin, 5-fluorouracil, and leucovorin. FOLFOX4 is today one of the most commonly used chemotherapy regimens for advanced colorectal cancer, and many experts consider it the first-line choice.
Bevacizumab received approval from the Food and Drug Administration last year for treatment of advanced colorectal cancer when used in combination with irinotecan plus 5-fluorouracil and leucovorin, the other commonly used chemotherapy combination for this type of cancer.
The new results “show that bevacizumab is effective when it's given with a drug that is not irinotecan,” commented Robert J. Mayer, M.D., director of the Center for Gastrointestinal Oncology at the Dana-Farber Cancer Institute in Boston.
But because the new study was done in previously treated patients (they had all failed treatment with irinotecan and 5-fluorouracil), it's inappropriate to view the results as a basis for using bevacizumab plus FOLFOX4 on previously untreated patients, cautioned Bruce J. Giantonio, M.D., lead investigator of the study and an oncologist at the University of Pennsylvania in Philadelphia. The results raise the possibility of using bevacizumab plus FOLFOX4 as first-line therapy, “but that approach needs further study,” he said.
Bevacizumab is marketed by Genentech as Avastin. The current study was sponsored by the National Cancer Institute and run by the Eastern Cooperative Oncology Group. Genentech provided the bevacizumab used in the study.
Patients with advanced colorectal cancer who had previously been treated with irinotecan and 5-fluorouracil were randomized to one of three study arms: FOLFOX4 alone, 10 mg/kg of bevacizumab given intravenously once every 2 weeks, or both regimens. The study's primary outcome was overall survival. Full results on the 249 patients who were treated with bevacizumab alone have not yet been reported, but this arm of the study was closed prematurely because of a trend toward worse outcomes, Dr. Giantonio said.
After a median follow-up of 18.4 months, the 290 patients treated with both bevacizumab and FOLFOX4 had a median survival rate of 12.5 months, compared with a 10.7-month median survival rate among the 289 patients who were treated with FOLFOX4 alone, a statistically significant difference.
A hazard ratio analysis showed that adding bevacizumab cut mortality by 26% compared with using FOLFOX4 alone, he reported at the symposium, also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiation and Oncology, and the Society of Surgical Oncology.
The combination regimen was also generally well tolerated compared with FOLFOX4 alone, Dr. Giantonio said. The combination produced a larger number of certain grade 3 toxicities: neuropathy, hypertension, bleeding, nausea, and vomiting.