mCRPC Treated with Concomitant ADT and Radium-223 Therapy - Episode 2
Daniel J. George, MD:In this case, when the patient started to progress on hormonal therapy, his PSA rose rapidly. That’s one of the indications of somebody who’s going to develop overt metastatic disease. So, when his PSA got up to 15 ng/mL with a rapid doubling time, that was a good indication to do scans. Again, he shows evidence of new metastatic disease in his bone scan and his CT scan. At that point in time, he’s relatively asymptomatic with metastatic disease primarily in his bones. His treatment options include secondary hormonal therapy, with drugs like abiraterone or enzalutamide or immunotherapy with a drug like sipuleucel-T.
The patient had a relatively rapid course of disease. A couple of years after his surgery, his disease rapidly rose in PSA. His hormonal therapy response was relatively brief. You could argue this patient has a fairly aggressive course of disease. And yet, being minimally symptomatic with bone-only metastatic disease, his life expectancy is still probably in the 2- to 3-year range. To me, that’s still a reasonable patient to consider for sipuleucel-T. The best patient for sipuleucel-T is a patient with low volume and relatively low PSA. In retrospective series, that has shown the longest absolute benefit associated with sipuleucel-T.
When we give sipuleucel-T, we’re essentially giving the patient an immune stimulant. It’s an autologous cellular therapy that works to activate the patient’s own immune system to overcome tolerance and to regulate and recognize the prostate cancer. It doesn’t work quickly, so in many cases, we’ll administer sipuleucel-T and then quickly move on to another therapy. But that doesn’t mean it’s not working. It continues to work in that patient over the next 2- to 3-year period of time. So, in this patient, we would have considered adding sipuleucel-T with those early rises in PSA up to the 15 ng/mL range. Once he got up to 145 ng/mL and was becoming more symptomatic, that window for sipuleucel-T was probably closed. For this particular case, there was a relatively narrow window in which we would have considered the therapy.
When we administer abiraterone and prednisone, we’ll do so in the context of castration-resistant prostate cancer. That’s defined by maintaining a low testosterone levelless than 50 ng/dL, typically—and still having evidence of disease progression, typically with a rise in PSA, but maybe changes on a bone scan or a CT scan as well. All the studies done with abiraterone/prednisone in this setting that have led to their FDA approval have been done in patients who have maintained that castrate level of testosterone.
We don’t really know if abiraterone/prednisone will work as well if we don’t maintain that low testosterone level. The best way to do that is to keep the patient on their LHRH agonist, if that’s what they’re on, or if they’ve had surgical castrationwhatever method we’re using to maintain that low testosterone. It’s possible that off those therapies, the patients’ testosterone levels will still stay low and we can get by with just abiraterone and prednisone, but that’s not recommended. The on-label use for those drugs is with concomitant androgen suppression therapy.
Transcript edited for clarity.