A Randomized Phase II Trial of Short-Course Androgen Deprivation Therapy With or Without Bevacizumab for Patients With Recurrent Prostate Cancer After Definitive Local Therapy.

PURPOSE - Patients with recurrent prostate cancer after local treatment make up a heterogeneous population for whom androgen deprivation therapy (ADT) is the usual treatment. The purpose of this randomized phase II trial was to investigate the efficacy and toxicity of short-course ADT with or without bevacizumab in men with hormone-sensitive prostate cancer.

PATIENTS AND METHODS - Eligible patients had an increasing prostate-specific antigen (PSA) of ≤ 50 ng/mL and PSA doubling time of less than 18 months. Patients had either no metastases or low burden, asymptomatic metastases (lymph nodes < 3 cm and five or fewer bone metastases). Patients were randomly assigned 2:1 to a luteinizing hormone-releasing hormone agonist (bicalutamide or bevacizumab) or ADT alone for 6 months. The primary end point was PSA relapse-free survival (RFS). Relapse was defined as a PSA of more than 0.2 ng/mL for prostatectomy patients or PSA of more than 2.0 ng/mL for primary radiation therapy patients.

RESULTS - Sixty-six patients received ADT + bevacizumab and 36 received ADT alone. Patients receiving ADT + bevacizumab had a statistically significant improvement in RFS compared with patients treated with ADT alone (13.3 months for ADT + bevacizumab v 10.2 months for ADT alone; hazard ratio, 0.47; 95% CI, 0.29 to 0.77; log-rank P = .002). Hypertension was the most common adverse event in patients receiving ADT + bevacizumab (36%).

CONCLUSIONS - ADT combined with bevacizumab resulted in an improved RFS for patients with hormone-sensitive prostate cancer. Long-term follow-up is needed to determine whether some patients have a durable PSA response and are able to remain off ADT for prolonged periods. Our data provide rationale for combining vascular endothelial growth factor-targeting therapy with ADT in hormone-sensitive prostate cancer.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Apr 04 [Epub ahead of print]

Rana R McKay, Amado J Zurita, Lillian Werner, Justine Y Bruce, Michael A Carducci, Mark N Stein, Elisabeth I Heath, Arif Hussain, Hai T Tran, Christopher J Sweeney, Robert W Ross, Philip W Kantoff, Susan F Slovin, Mary-Ellen Taplin

Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY., Rana R. McKay, Lillian Werner, Christopher J. Sweeney, Philip W. Kantoff, and Mary-Ellen Taplin, Dana-Farber Cancer Institute, Boston; Robert W. Ross, Bluebird Bio, Cambridge, MA; Amado J. Zurita and Hai T. Tran, MD Anderson Cancer Center, Houston, TX; Justine Y. Bruce, University of Wisconsin Carbone Cancer Center, Madison, WI; Michael A. Carducci, Johns Hopkins University; Arif Hussain, Greenebaum Cancer Center, Baltimore, MD; Mark N. Stein, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Elisabeth I. Heath, Karmanos Cancer Institute, Detroit, MI; and Philip W. Kantoff and Susan F. Slovin, Memorial Sloan Kettering Cancer Center, New York, NY.