Dr. van den Bent, professor of neuro-oncology at the cancer center of Erasmus University in Rotterdam, the Netherlands, charged that Duke has a history of doing uncontrolled trials, but he also criticized the field's eagerness to embrace bevacizumab based on such trials.
“The use of bevacizumab at present is based on uncontrolled studies; it's been FDA approved on a scientifically not valid end point,” said Dr. van den Bent, a past chair of the EORTC (European Organisation for Research and Treatment of Cancer) Brain Tumor Group.
Study design also triggered a complaint with the RTOG trial. Dr. Gilbert cautioned that randomization was not consistent because of safety concerns with the temozolomide regimen. Until these were resolved, the initial 90 patients were randomized 2:1 favoring irinotecan. Consequently, the final 30 temozolomide patients were assigned to that arm without randomization.
For these reasons, “we cannot on the basis of this study tell which of the two treatments” is better, “or in fact whether a combination of chemotherapy with bevacizumab is better than bevacizumab alone,” he said, stressing that the study was not powered for comparison.
A member of the audience asked whether this wasn't “kind of a charade,” since comparisons were being made anyway.
“It's not a charade,” Dr. Gilbert replied, reiterating that the investigators had two separate goals: safety with temozolomide and efficacy with irinotecan. “It is what it is,” he said. “We certainly weren't going to power it, because we weren't interested particularly in the question of which was the better regimen.”
Genentech sponsored the study from Duke University. Dr. Desjardins reported no conflicts of interest. Dr. Gilbert disclosed research support from Merck and Genentech, and honoraria/advisory board participation with Merck and Genentech. Dr. van den Bent said he is a consultant for eight companies, including F. Hoffmann-La Roche, parent company of Genentech.