Patients with advanced non-small cell lung cancer (NSCLC) lived twice as long when they received an indirect angiogenesis inhibitor plus docetaxel instead of docetaxel alone, interim results of a randomized trial showed.
The preliminary results showed a median overall survival of 11.1 months in patients treated with docetaxel and bavituximab compared with 5.6 months in patients who received only docetaxel.
Progression-free survival (PFS) did not differ between treatment groups, although treatment with bavituximab was associated with a trend toward a longer disease-free interval, as reported at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology.
The objective response rate also trended higher in the bavituximab arm.
“In this phase II trial, a positive trend favoring bavituximab was noted across all efficacy endpoints,” said David E. Gerber, MD, associate professor of Internal Medicine at the University of Texas Southwestern Medical Center in Dallas and the study’s lead author. “Interim results demonstrate median overall survival differences and significant overall survival hazard ratios favoring bavituximab-containing arms. These effects do not appear limited to any subset of patients.”
Bavituximab is a monoclonal antibody that targets phospholipid phosphatidylserine (PS). Normally, PS in vascular endothelial cells is limited to the inner membrane leaflet. However, exposure to the tumor microenvironment flips PS to the outer membrane leaflet, Gerber explained.
When exposed on the outer membrane leaflet, PS suppresses antitumor immune responses. Bavituximab binds to exposed PS and reactivates the immune response, shutting down tumor vascular processes.
Gerber presented interim results from a randomized trial comparing docetaxel paired with two different doses of bavituximab (1 mg/kg or 3 mg/kg weekly) versus docetaxel and placebo. Eligible patients had stage IIIB/IV NSCLC that had progressed after treatment with platinum-based chemotherapy.
Investigators randomized 117 patients 1:2 to the control arm or the two bavituximab arms. The primary endpoint was objective response rate. Secondary endpoints included PFS, overall survival, safety, and duration of response.
The objective response rate was 8% (3 patients) in the control arm, 15% (6 patients) in the 1 mg/kg arm, and 18% (7 patients) in the 3 mg/kg arm. Stable disease occurred in 19 (50%), 22 (55%), and 20 % (51.3%) of patients in the control, 1 mg/kg, and 3 mg/kg arms, respectively.
PFS was 3 months, 4.2 months, and 4.5 months in the control, 1 mg/kg, and 3 mg/kg arms, and overall survival was 5.6 months in the control arm, 11.1 months in the 1 mg/kg arm (P
= .0286), 13.1 in the 3 mg/kg arm (P
= .0714), and 12.1 months in the combined bavituximab arms (P
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