Docetaxel Combined With Bavituximab in Previously Treated, Advanced Nonsquamous Non-Small-Cell Lung Cancer.
Bavituximab is a phosphatidylserine-targeting antibody with a selective tumor, vascular-directed immune response. In this phase II trial the efficacy and safety of bavituximab combined with docetaxel for previously treated, advanced nonsquamous non-small-cell lung cancer were evaluated.



Patients were randomized 1:1:1 to receive docetaxel 75 mg/m(2) every 21 days for up to 6 cycles combined with weekly, blinded infusions of placebo, bavituximab 1 mg/kg, or bavituximab 3 mg/kg until disease progression or unacceptable toxicity. The primary end point was overall response rate (ORR), with a predefined end point of 26% in the bavituximab arms. After study unblinding, vial-coding discrepancies were discovered in the placebo and bavituximab 1 mg/kg groups. In exploratory analyses, data from these groups were pooled to form the control group and compared with the 3 mg/kg group.



Efficacy end points in the bavituximab 3 mg/kg group (n = 41) and in the placebo/bavituximab 1 mg/kg group (n = 80), respectively, were as follows: ORR, 17.1% (95% confidence interval [CI], 5.6%-28.6%) and ORR, 11.3% (95% CI, 4.3%-18.2%); median progression-free survival 4.5 and 3.3 months (hazard ratio [HR], 0.74 [95% CI, 0.45-1.21]; P = .24); median overall survival 11.7 and 7.3 months (HR, 0.66 [95% CI, 0.40-1.10]; P = .11). Toxicities were manageable and similar between arms.



The combination of bavituximab and docetaxel is well tolerated. Although no firm efficacy conclusions can be drawn and the trial did not meet the predefined primary end point, exploratory analyses suggest trends favoring the combination of bavituximab 3 mg/kg with docetaxel. This regimen is being evaluated in the ongoing, global, phase III SUNRISE trial.
Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: david.gerber@utsouthwestern.edu.
David E
DE
Gerber
Tennessee Oncology, PLLC, Nashville, TN.
David R
DR
Spigel
Medulla Chemotherapy and Immunotherapy Clinic, Tbilisi, Republic of Georgia.
David
D
Giorgadze
Ironwood Cancer and Research Center, Chandler, AZ.
Mikhail
M
Shtivelband
Kyiv City Oncology Hospital, Kyiv, Ukraine.
Olga V
OV
Ponomarova
Peregrine Pharmaceuticals, Inc, Tustin, CA.
Joseph S
JS
Shan
Peregrine Pharmaceuticals, Inc, Tustin, CA.
Kerstin B
KB
Menander
Pennsylvania State Hershey Cancer Institute, Hershey, PA.
Chandra P
CP
Belani
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D000077143:Docetaxel; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D043823:Taxoids; D000077143:Docetaxel; C547825:bavituximab
Immunotherapy; Macrophages; Monoclonal antibody; Phosphatidylserine; Tumor microenvironment