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

J Clin Oncol. 2016 Jun 1;34(16):1913-20. doi: 10.1200/JCO.2015.65.3154. Epub 2016 Apr 4.

Abstract

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 and 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%).

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / therapeutic use*
  • Bevacizumab / administration & dosage*
  • Bevacizumab / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • Androgen Antagonists
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Prostate-Specific Antigen