Overall survival was twice as long (average of 11-13 months) in patients with advanced lung cancer who received bavituximab compared with patients who did not receive the drug (average 5.6 months), according to research presented at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology by David Gerber, MD, of the University of Texas Southwestern Medical Center.
Bavituximab is a monoclonal antibody that targets phosphatidylserine, which is found in the membranes of cells throughout the body, including those that line blood vessels. Normally phosphatidylserine is inside cell membranes and inaccessible to antibodies, but, under stressful conditions such as the tumor microenvironment, phosphatidylserine moves to the outer surface of the membrane and becomes accessible to antibodies in the blood of tumor blood vessels.
Bavituximab can trigger the destruction of tumor blood vessels. It also may harness the immune system. When the blood supply of tumors has exposed phosphatidylserine, the tumors can evade an immune response. This evasion happens because, normally, exposed phosphatidylserine marks cells that are dying, and those cells get ignored by the immune system. The researchers hoped to learn if bavituximab binding to phosphatidylserine would signal the immune system to attack tumor blood vessels that have exposed phosphatidylserine.
The double-blind, placebo-controlled, phase II trial randomly assigned 117 patients to 1 of 3 treatment groups: docetaxel plus placebo, docetaxel plus a low dose of bavituximab, or docetaxel plus a higher dose of bavituximab. The patients had all received initial chemotherapy previously.
Bavituximab added to docetaxel improved both tumor shrinkage (15% and 18% of the low- and high-dose bavituximab arms, respectively, had their tumors shrink vs 8% of the docetaxel plus placebo arm) and progression-free survival (approximately 4.5 months in both bavituximab arms vs 3 months in the docetaxel plus placebo arm).
The improvement in survival with bavituximab “is persistent and most pronounced after a few months,” explained Gerber. He stated that this suggests that the therapeutic benefit may be caused, at least in part, by an immune response.
A phase III trial in a larger group of lung cancer patients is planned. Bavituximab, in combination with other treatments, is also being tested in breast, rectal, liver, and prostate cancer.
The trial was sponsored by Peregrine Pharmaceuticals, Inc., who is the drug’s manufacturer.