Results from the RADAR clinical trial presented at the 2018 ASCO Genitourinary Cancer Symposium indicate that 18 months of ADT could very likely become the new standard of care. The RADAR trial demonstrated that 18 months of androgen deprivation therapy (ADT) is significantly better than 6 months of ADT at staving off prostate cancer progression and mortality in men with locally advanced prostate cancer, in combination with radiation therapy (RT).
ADT remains a cornerstone of treatment for high-risk localized and advanced prostate cancer, and acts to suppress androgens – the male hormones that are the primary fuel for prostate cancer. In localized and locally advanced prostate cancer, ADT is typically combined with radiotherapy (RT) to the prostate area. Patients typically receive ADT for two to three years, based on previous clinical trials that established that long-term ADT (28-36 months) is more effective than short term ADT (4-6 months). However, long-term ADT is associated with significant side effects, including sexual dysfunction, weight gain, loss of bone density and fractures, depression, and myocardial infarctions.
“We are looking to try to determine what would be the best length of hormone suppression,” said Dr. David Joseph, of Sir Charles Gairdner Hospital, Australia, who presented the RADAR trial results. “We wanted to develop a treatment which we’d be happy for a loved one or friend to receive. One that has side effects no worse than short course– 6 months, and is as effective as long course –36 months. We chose (to test) 18 months — in between.”
Dr. Joseph and colleagues conducted the RADAR trial, a randomized phase 3 clinical trial that compared an intermediate length of 18 months of ADT plus RT vs. 6 months of ADT plus RT in 1,071 men with locally advanced prostate cancer.
A second aim of the trial was to test the hypothesis that zoledronic acid, a treatment that increases bone density and has some anti-cancer activity, would improve efficacy of either treatment strategy. Thus, half of the men in each ADT treatment group received zoledronic acid for 18 months.
After ten years of follow-up, the trial found that 18 months of ADT was significantly more effective than 6 months of ADT; distant progression was reduced by 29% and death from prostate cancer was reduced by 30%. 18 months of ADT was also associated with reduced local progression (by 40%), reduced PSA progression (by 35%), reduced secondary therapeutic intervention (by 34%), and reduced transition to castration resistance (by 37%), compared with 6 months of ADT. The addition of zoledronic acid to either length of ADT had no clear effect.
“What about quality of life? For this significant improvement, there was a relatively small price to pay (with the longer term of ADT),” said Joseph. “These patients did have an early slight reduction in quality of life, but by a short period, there was very little difference in outcome on all measures.”
Results from another phase 3 trial presented at the 2017 Annual ASCO Meeting found that in patients with high risk prostate cancer, 18 months of ADT was as effective as 36 months of ADT, but with far less side effects.
Based on the results from these trials, “we think this is highly suggestive that 18 months (of ADT) looks like a good bet,” Joseph concluded.
“What this means for patients, is that we can now confirm that short-term hormone therapy, for 4-6 months is not enough for men with high risk prostate cancer. Furthermore, another trial from Canada that was presented last year at ASCO demonstrated that 18 months of hormone therapy appeared similar in efficacy to 36 months, but had significantly less side effects,” said Daniel Spratt, MD, a PCF Young Investigator and Vice Chair and Chief of the Prostate Radiotherapy Program at the University of Michigan, who was not involved in the study. “The combination of these two exciting trials is that 18 months will likely become the new standard of care for many high-risk prostate cancer patients, especially those with comorbidities or men who are experiencing above average side effects while on hormone therapy.”