Preliminary results of a phase III trial for advanced pancreatic cancer suggest that addition of bevacizumab to gemcitabine does not improve survival compared with treatment with gemcitabine alone, according to a presentation at the 2007 Gastrointestinal Cancers Symposium.

“These results were quite disappointing. Our prior phase II study suggested that bevacizumab in combination with gemcitabine is an active combination in pancreatic cancer patients,” said Hedy Lee Kindler, MD, Associate Professor of Medicine and Director of the Gastrointestinal Oncology Program at the University of Chicago, and the study’s lead author. “Unfortunately, given the number of negative phase III trials that have followed promising phase II trials in this disease, this result is not altogether surprising.”

This randomized, double-blind placebo-controlled trial enrolled 602 patients with metastatic or locally advanced pancreatic cancer, with 302 patients receiving gemcitabine and bevacizumab and 300 patients receiving gemcitabine and placebo. The two groups were balanced in terms of gender, age, stage of disease, and performance status.

Median overall survival was 5.7 months for the bevacizumab group versus 6.0 months for the placebo group, an insignificant difference. Both groups experienced the same side effects, including lowered blood counts, blood clots, and stroke. Patients who received bevacizumab had higher rates of high blood pressure and slightly higher rates of bowel perforation and gastrointestinal bleeding.

“This trial definitively shows that bevacizumab does not improve survival in patients with advanced pancreatic cancer,” Kindler said. “The many laboratory correlative studies that were a part of this study may help us determine if there is a subset of patients who might still benefit from bevacizumab, and further insights may be obtained in ongoing studies in advanced disease in which bevacizumab is being combined with endothelial growth factor receptor (EGFR) inhibitors, and in the adjuvant setting where it is being combined with radiation.”

The current standard of care for advanced pancreatic cancer is gemcitabine or gemcitabine with erlotinib, but these drugs have a very modest impact on survival. Given the difficulty of successfully treating pancreatic cancer, other agents are being actively investigated. The trial was conducted by Cancer and Leukemia Group B, a national clinical trial research group.