Transcript:Charles J. Ryan, MD: In the COU-AA-302 study, there were a number of patients who were over the age of 75, and prostate cancer is a disease that affects, in general, men as they age. And, so we thought with great interest that it would be important to look at elderly patients which, in this case, we defined as 75 years or older. My colleague, Matthew Smith, published a paper demonstrating that in the patients who were 75 years or older, there was a retained benefit from abiraterone and prednisone compared to prednisone alone. There was still a benefit over prednisone alone. Just because patients were over this age of 75, they continued to live longer when they took the abiraterone plus prednisone compared to the prednisone alone. And the hazard ratio was actually 0.71 for the elderly patients, whereas it was 0.81 for the patients who were younger. So, if anything, it’s maybe even a slightly better outcome.

Now, the elderly patients did have slightly more side effects that were related to edema and fluid retention, probably a manifestation that this is something that is simply more common in elderly patients. But I think the takeaway message from that paper was that it’s perfectly safe to administer to elderly patients, provided you are monitoring them as you would anybody.

With respect to steroids, one of the major concerns is whether patients are going to develop issues around diabetes, cataracts, and/or stomach ulcers, and/or weight gain. And in the Fizazi paper, a number of variables were looked at. In fact, this was done a couple of different times. The Fizazi paper combined both of the studies with abiraterone and demonstrated that really the incidence of the two most common steroid side effects, weight gain and hyperglycemia, is still relatively low. The hyperglycemia was around 7% or 8%, and significant weight gain was only about 3% to 5%. So, it’s not a really significant problem in these patients. When broadly defined, corticoid steroid-related adverse events did occur in about 25% of the patients overall.

The term ‘steroids’ is a little bit complicated, honestly, and especially to a general non-medical public. People get a little bit confused. So, there’s a couple of points worth making. We’re talking first of all about a corticosteroid and we’re talking about prednisone, which is essentially given at a dose of 10 mg; essentially corticosteroid replacement doses. We are not giving super physiologic doses of steroids like we would for a person who’s having an allergic or an excess immune problem. And so, we’re not seeing, for example, Cushingoid, or patients developing some of the toxicities that are associated with high-dose steroids.

So, first, these are corticosteroids, not anabolic steroids, right? And it’s important for patients to understand that ‘steroids’ is a very general term. Second, these steroids are really not that much greater in dose than our body makes normally every day anyway. And, third, with proper monitoring, I think that it’s something that is very controllable. I would add finally that in patients who do have some corticosteroid-related toxicity, it is reasonable to lower the dose of the corticosteroid from 5 mg twice/day to 5 mg/day, sometimes 7.5 mg/day. This was allowed in the protocol that led to the approval, and many patients did undergo a steroid dose reduction. We just reported a 140-patient study in which patients took only 5 mg of steroids and did just fine. And so, I think that it’s up to the physician to ask the question, does the patient need the 10 mg? Are they benefitting from the 10 mg? Should I reduce the dose? And if so, they can do so with confidence as long as they continue to monitor the patient.

Transcript Edited for Clarity