A phase II randomized trial found that combining a short course of androgen deprivation therapy (ADT) with the angiogenesis inhibitor bevacizumab improved relapse-free survival (RFS) in men with hormone-sensitive prostate cancer. Results of the trial are published in the Journal of Clinical Oncology.
“Treatment with short-term ADT plus bevacizumab was feasible, although it was associated with more toxicity than ADT alone in hormone-sensitive prostate cancer,” wrote study author Mary-Ellen Taplin, MD, director of clinical research at the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, and colleagues.
The study included 102 patients with hormone-sensitive, recurrent prostate cancer randomized to ADT plus the vascular endothelial growth factor (VEGF)-inhibiting antibody bevacizumab (n = 66) or to ADT alone (n = 36).
While the addition of bevacizumab to docetaxel has not been shown to improve overall survival in previous studies of men with castration-resistant prostate cancer, the current trial was the first to explore the role of bevacizumab in earlier stage prostate cancer.
All patients on trial had disease recurrence in the form of rising prostate-specific antigen (PSA) levels and a PSA doubling time of less than 18 months. Prior ADT was allowed if it was administered for 8 months or less and the patient’s testosterone levels had recovered. The primary endpoint was RFS. Relapse was defined as a PSA of more than 0.2 ng/mL for patients who had a radical prostatectomy and a PSA of more than 2.0 ng/mL for those who received primary radiation therapy.
“When compared with ADT, the addition of bevacizumab resulted in a statistically significant improvement of RFS and improved 1-year RFS,” the authors wrote.
Patients who received the ADT plus bevacizumab combination therapy had a 3.1-month improvement in RFS compared with those who received ADT alone (13.3 months vs 10.2 months; hazard ratio, 0.47; P = .002).
ADT is the current mainstay therapy for men with non-metastatic prostate cancer or those with low-volume metastatic disease.
The most common adverse event in the ADT plus bevacizumab arm was hypertension (36% of patients). Sixty-nine percent of patients in the combination therapy arm experienced a grade 2 or higher adverse event.
Other adverse events included musculoskeletal pain, infection, and headache. Among patients who received ADT plus bevacizumab, total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein significantly increased at 3 months and at the end of treatment compared to levels at the start of trial. About 20% of patients treated with ADT plus bevacizumab experienced grade 3 adverse events.
Further follow-up of patients is necessary to understand whether the PSA responses among some patients remain durable without the need for further therapy.
The results, wrote the authors in their discussion, suggest that further studies of anti-VEGF therapies combined with ADT should be explored to promote a long-term response to ADT.