Judd W. Moul, MD: Apalutamide is a novel oral antiandrogen that is under consideration by the FDA for treatment of M0 CRPC. The chemical name is ARN-509, which would be its research name, and it’s under development by Janssen Pharmaceuticals. It has been looked at in phase II trials, and they were very promising, by Matthew Smith and his colleagues. Matt is a well-known medical oncologist in Boston and was the principal investigator on the phase II trial of apalutamide, which gave a strong signal of its safety and effectiveness.
The drug was well tolerated. Less than 15% of patients in the phase II trial had to go off the drug for side effects. So, more than 85% of patients stayed on the drug. The PSA response in the phase II trial was almost 90%, meaning that more than 90% of patients had a greater than 50% PSA response. A significant number of men, almost half of those men, were able to stay on apalutamide for at least 2 years in the setting of M0 castration-resistant prostate cancer. And this has led to a subsequent phase III randomized controlled trial that is now essentially enrolled and has been submitted to the FDA.
The phase III clinical trial for apalutamide is called the SPARTAN trial. It was initiated in 2013, and recently Janssen had a press release saying that the trial met its primary endpoint of delaying progression to metastatic disease. Again, these gentlemen had M0 castration-resistant prostate cancer. The primary endpoint of the phase III trial was progression to metastatic disease, and the press release states that the trial was positive, meaning that the drug apalutamide had a statistically significant benefit compared to placebo in delaying the time to metastatic disease. And because of the trial being positive, they have submitted an application to the FDA for consideration of apalutamide receiving FDA approval specifically for men with M0 CRPC.
Julie Graff, MD: The SPARTAN study looks at nonmetastatic castration-resistant prostate cancer. That typically means a rise in PSA without any tumors seen on a bone scan or a CAT scan. Part of the reason we have this space in prostate cancer is because our imaging studies don’t look for, or they can’t find, tumors that are smaller than a pea. So, we have this space where we can’t see anything on our typical scans. The patient might have grains of sand here and there, but there’s something in there. No other organ makes PSA.
The SPARTAN study looked at these patients who had a PSA doubling time of shorter than 10 months and randomized them to placebo versus apalutamide, and the primary endpoint was metastasis-free survival. So, these patients did not have PSAs checked. They had imaging studies checked, and all the imaging studies were reviewed by a central reviewer to look for new metastatic disease. And that time was measured.
Charles J. Ryan, MD: The Rathkopf study, which was published in the Journal of Clinical Oncology in 2013, demonstrated a high degree of clinical activity of apalutamide, which was previously known as ARN-509. In that study, we looked at a variety of doses and found it to be generally safe for oral administration on a long-term basis. We also found that a high number of patients, about 50% of all patients on the study, experienced a 50% decline in their PSA or greater. However, some of those patients had abiraterone resistant disease and, therefore, would not have a high likelihood of responding to apalutamide.
In the nonmetastatic setting in which this has been explored in a phase II study, the number of patients who experienced a PSA decline of 50% or greater was much higher. I think it was well over 80%. In summary, apalutamide is a well-tolerated, orally available, next-generation androgen receptor antagonist.
Transcript Edited for Clarity