(ChemotherapyAdvisor) – Combining the novel monoclonal antibody bavituximab with docetaxel chemotherapy was found to nearly double response rates in patients with previously treated locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) when compared with placebo plus docetaxel, according to interim results reported at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology.
The phase 2 study randomly assigned 121 patients to docetaxel 75mg/m2 every 21 days and either placebo (n=40), bavituximab 1mg/kg (n=40), or bavituximab 3mg/kg (n=41) weekly for up to 6 cycles, said lead study author David Gerber, MD, of the Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX.
Bavituximab, directed against phosphatidylserine, “has been shown to localize selectively to tumor vasculature, synergize with chemotherapy, cause vascular shutdown in tumors, and reactivate innate and adaptive tumor immunity,” he reported.
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Based on 117 evaluable patients, objective response rate (ORR), the primary end point, was 7.9% for the docetaxel plus placebo arm, 15.0% for the docetaxel plus bavituximab 1mg/kg arm (P=0.3262), and 17.9% for the docetaxel plus bavituximab 3mg/kg arm (P=0.1895). Pooling the bavituximab arms resulted in an ORR of 16.5 months (P=0.2069). Stable disease was observed in 50% of patients in the placebo arm, 55% in the bavituximab 1mg arm, 51.3% in the bavituximab 3mg/kg arm, and 53.2% in the pooled bavituximab group.
By central review, median progression-free survival was 3.0 months in the placebo arm, 4.2 months in the bavituximab 1mg/kg arm (HR, 0.571; P=0.0794), 4.5 months in the bavituximab 3mg/kg arm (HR, 0.65; P=0.1921), and 4.2 months for the pooled group (HR, 0.605, P=0.067).
The study was unblinded at 18 months, at which point median overall survival (OS) was 5.6 months in the placebo arm, 6.7 months in the bavituximab 1mg/kg arm (HR, 0.512; P=0.0286), and 5.2 months in the bavituximab 3mg/kg arm (HR, 0.539; P=0.0714); for the pooled group, median OS was 12.1 months (HR, 0.524; P=0.0154). Subgroup analysis for OS favored bavituximab for all factors (eg, age, gender, race, ECOG performance status, adenocarcinoma vs other histologies).
The combination of docetaxel and bavituximab was well tolerated and there was no apparent increase in bleeding or thrombotic events. A confirmatory phase 3 trial is under development.
Dr. Gerber received research funding from Peregrine Pharmaceuticals, Inc.
The symposium is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and The University of Chicago.
