VEGF inhibitors show activity when combined

TAMPA, Fla. — A combination of sorafenib and bevacizumab is active in patients with epithelial ovarian cancer, according to data presented by Nilofer Azad, MD, a fellow at the medical oncology branch of the NCI.

“The hypothesis is that if you target an important pathway like VEGF with two different agents, there might be increased clinical benefit,” Azad said at the Society of Gynecologic Oncologists 39th Annual Meeting on Women’s Cancer.

The study included 15 patients with epithelial ovarian cancer who were enrolled in one of two cohorts. The patients started with half the single-agent doses of bevacizumab (Avastin, Genentech) and sorafenib (Nexavar, Bayer). Seven of the 15 patients had partial responses.

Azad suggested that the treatment was well tolerated despite almost all of the patients having at least grade-2 hypertension and hand–foot syndrome and the majority of patients undergoing a reduction in the dose of sorafenib. This reduction did not appear to affect therapy benefit, Azad said.

Although CA125 change was measured, this was not used as response criteria. After conducting a retrospective analysis, Azad said CA125 change would have excluded three of the responses and therefore may not be the best measure of response. – by Emily Shafer

There are important points to consider when combining therapeutic agents in solid tumors. First, are both compounds active individually? It does not make sense to combine things that are not active alone or for which there is no evidence of synergy, at least in animal models. Unfortunately, this combination of sorafenib and bevacizumab suffers from both of these points. Although bevacizumab has been identified as an active single agent, we do not have any evidence that sorafenib has any activity in epithelial ovarian cancer. The next question would be: Is the combination tolerable at relevant doses? There are significant overlapping toxicities allowing only half of the normal bevacizumab dose to be delivered and only a quarter of the sorafenib dose used in hepatocellular and renal cell cancer. Third, since this combination does have significant overlapping toxicities, maybe we should be giving these agents in sequence, assuming that sorafenib will someday show single-agent activity. Finally, the activity seen in this trial is difficult to separate from the single-agent activity of full-dose bevacizumab.

– Bradley Monk, MD

Associate Professor and Director of Research, Gynecologic Oncology
University of California Irvine Medical Center

For more information:

Azad N, Annunziata CM, Greenberg L, et al. #49. Presented at: the Society of Gynecologic Oncologists 39th Annual Meeting on Women’s Cancer; March 9-12; Tampa, Fla.