New Drug Improves Survival in Patients with Advanced Lung CancerPatients with advanced lung cancer who received the drug bavituximab lived twice as long as trial participants who did not receive the drug. These results , from a phase II trial, were presented at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology . Peregrine Pharmaceuticals, Inc., the drug’s manufacturer, sponsored the trial.
Bavituximab is a monoclonal antibody that targets a molecule called phosphatidylserine (PS) that is found in the membranes of cells throughout the body, including those that line blood vessels. In normal cells, PS is restricted to the inside of cell membranes, where it is inaccessible to antibodies. Under certain conditions, like those found in the stressful tumor microenvironment, PS moves to the outer surface of the cell membrane, explained the study’s principal investigator, Dr. David Gerber of the University of Texas Southwestern Medical Center. In the case of tumor blood vessels, this means that PS is exposed and accessible to antibodies in the blood.
Laboratory studies have shown that bavituximab can trigger the destruction of tumor blood vessels. The drug may also work by harnessing the immune system. Tumors supplied by blood vessels with exposed PS can evade an immune response. That’s because exposed PS normally marks cells that are in the process of dying, so the immune system ignores them. The researchers hoped to learn whether bavituximab, by binding to PS, would signal to the immune system to attack tumor blood vessels with exposed PS, explained Dr. Gerber.
In the double-blind, placebo-controlled trial, the researchers randomly assigned 117 patients to one of three treatment groups: docetaxel (Taxotere) plus placebo, docetaxel plus a low dose of bavituximab, or docetaxel plus a higher dose of bavituximab. All patients had previously received initial chemotherapy. The trial was unblinded 18 months after the first patient was enrolled.
The results showed differences in tumor shrinkage (15 and 18 percent of patients in the low and high bavituximab groups had their tumors shrink, versus 8 percent of those receiving docetaxel plus placebo) and progression-free survival (about 4.5 months in the two bavituximab arms, versus 3 months with docetaxel plus placebo).
The greatest differences were for overall survival; patients receiving docetaxel plus placebo lived an average of 5.6 months from the start of treatment, whereas patients receiving docetaxel plus the low or high dose of bavituximab lived for an average of 11 and 13 months, respectively.
These survival differences are not likely due to differences in treatment received after the trial, Dr. Gerber noted. Seeing a larger improvement in overall survival than in progression-free survival is unusual for drugs that target cancer cells directly, he added. Because the improvement in survival with bavituximab “is persistent and most pronounced after a few months,” that suggests that the therapeutic benefit may be caused, at least in part, by an immune response, he said.
The researchers are planning a phase III trial of bavituximab in a larger group of lung cancer patients. Bavituximab is also being tested in combination with other treatments in patients with breast, rectal, liver, and prostate cancer.