Neal D. Shore, MD
In separate talks at the annual meeting of the American Urological Association (AUA) in Atlanta, Georgia, Neal D. Shore, MD, updated his peers about a promising new treatment for prostate cancer and encouraged them to incorporate novel therapies into their practices.
Shore, of Atlantic Urology Clinics in Myrtle Beach, South Carolina, discussed the novel therapy enzalutamide (MDV3100), the first androgen receptor signaling inhibitor, and the results of the phase III AFFIRM trial.1
As medical director of his practice’s independent clinical research arm, the Carolina Urologic Research Center, Shore has participated in more than 200 trials, including studies of enzalutamide. His center was a high-enrolling site in the AFFIRM trial, which was stopped in November 2011, after the drug improved overall survival in patients with metastatic castrate-resistant prostate cancer (mCRPC) who had failed docetaxel. Shore now serves as global primary investigator for the phase II TERRAIN trial evaluating the drug in the pre-chemotherapy setting in patients with mCRPC.
In addition to speaking about enzalutamide, Shore took time to advise his colleagues about the growing role urologists can play in seeing patients through their experience with a disease that is quickly becoming more treatable, particularly in advanced stages. It makes sense for urologists to understand and administer the newest treatments for prostate cancer, he said, since they are the doctors most likely to diagnose the disease and to follow patients long-term, even during their treatment by medical or radiation oncologists.
“These are all really very brand-new therapies, so there’s a learning curve that anyone interested in working with these patients can achieve,” said Shore, who has also participated in studies of abiraterone (Zytiga, Janssen Biotech, Inc) and sipuleucel-T (Provenge, Dendreon). “Read the literature, and partake in educational courses offered by the AUA, the American Society of Clinical Oncology, the Society of Urologic Oncology (SUO), and the Large Urology Group Practice Association as well as symposia offered at sectional, regional, and national meetings. If you have an interest, there’s no reason you should not be able to become familiar, knowledgeable, and comfortable in offering these therapeutics to your patients.”
Enzalutamide seems poised to become an exciting addition to the growing list of novel therapies approved for the treatment of prostate cancer, Shore told the audience. He explained that the drug is notable because it is orally administered once a day with or without food, drives a significant improvement in overall survival in trial participants, has an excellent safety profile, and works through distinct mechanisms of action.
The AFFIRM trial of enzalutamide, Shore said, demonstrated the largest overall survival benefit ever recorded in a post-chemotherapy setting for mCRPC.
The multinational trial included 1199 patients at 156 sites in 15 countries. Patients were randomized in a double-blind, prospective fashion; two out of three received enzalutamide 160 mg once a day, and the rest received placebo. The primary endpoint was overall survival.
The study was stopped early in November 2011 because it had demonstrated a significant 4.8-month improvement in overall survival. The hazard ratio was 0.631, which translates to a 37% reduction in risk of death for patients taking enzalutamide compared with those getting placebo (18.4 months vs 13.6 months; P
“Once patients progressed, they were allowed to go onto additional approved treatments such as cabazitaxel, abiraterone, or docetaxel, and what’s interesting is that the patients on the enzalutamide arm stayed on their drug therapy more than five months longer. The median was 8.3 months on enzalutamide versus three months on placebo,” Shore said. “Also really interesting was the fact that, in the enzalutamide arm, 54% of patients had more than a 50% decrease in their baseline PSA, and approximately 25% had more than a 90% decrease in their PSA from baseline.”
The drug was also extremely well tolerated among patients in the trial, Shore noted.
Overall, he said, the number of discontinuations due to adverse events was slightly higher in the placebo arm than in the enzalutamide arm, at 9.8% versus 7.6%. There was a slight increase in all grades of fatigue for patients on enzalutamide versus placebo of 33.6% versus 29.1%. But for very severe grades of fatigue, more was noted with placebo, at a rate of 7.3% versus 6.3%. In terms of any cardiac or liver function abnormalities, there was no significant difference in percentages in either arm. There were five (0.6%) reported cases of patients having had seizures in the enzalutamide arm.