Metastatic Hormone-Sensitive Prostate Cancer Progression to CRPC - Episode 6
Jorge Garcia, MD:Obviously, radium 223 has a unique mechanism of action, which I’m not sure that we really understand. I think it’s an alpha emitter, obviously, so it’s a radionucleotide-based approach, which is different from the old beta emitters. It has a short penetrance. It tackles the bone. Again, as I alluded to you before, 80% to 90% of men with prostate cancer will develop bone metastases. I think the questions that we have with radium 223 are: No 1, undoubtedly, the use of radium 223 can make people live longer.
Secondly, the problem with radium 223, to some extent, is that radium 223 doesn’t have the impact of typical agents that we use in prostate cancer, meaning that only 16% of the patients on radium 223 will have PSA declines. There is not a sense as to how often you should image patientsor for that matter, what the impact of a radionucleotide-based approach with regard to imaging is. How do you define if a patient is benefitting on treatment when your PSA [prostate-specific antigen level] keeps going up? So when I think of radium 223, mechanistically speaking, I tell my patients the goal of radium 223 is to help make them live longer, delaying the progression of bone metastases, and delaying what we call the skeletal-related events or skeletal symptomatic events. But we cannot define efficacy on therapy based upon your PSA level, which is the traditional marker that a lot of patients and physicians will pay attention to.
The ALSYMPCA data, which is the phase III data that led to the FDA approval, at least in the United States, of radium 223 actually used 2 different patient populations. They randomized patients with metastatic castration-resistant prostate cancer with predominance of bone metastases in the absence of visceral disease to receive either radium 223 or placebo plus the best supportive care at the time or the best standard of care.
I think the important point is that those patients actually were allowed to have received prior chemotherapy. So we have 2 buckets: some who have received prior chemotherapy, and some who were chemotherapy-naïve. If you look at the data as a whole, there was a benefit for all comers receiving radium 223 compared [with] those men who did not get radium 223. So you’ll find 2 buckets of patients or 2 buckets of practice in the United States. Some people believe that radium 223 should be given after chemotherapy. Some people believe that radium 223 could be given before chemotherapy. I tend to believe that since you need at least 6 cycles of radium 223 to really see that improvement in outcome, it is very hard for me to believe that a patient who has seen oral therapy, chemotherapy No 1, chemotherapy No 2, can go on to receive 6 months of radium223an agent that, to some extent, may not have those direct benefits of PSA level decline and a rapid improvement of symptomatic disease if one has symptomatic disease. So I tend to prefer radium 223 a bit earlier. But again, as I alluded to before, it totally depends on what sequence you have seen before. If you have ADT [androgen deprivation therapy]chemotherapy up front, then you may be able to get radium 223 earlier. On the contrary, if you haven’t seen chemotherapy and you saw oral therapy, it is possible, and most patients will go for an oral therapy to chemotherapy and then sequence radium 223 at some time between first-line chemotherapy and second-line chemotherapy.
Transcript edited for clarity.
Case: Met HSPCa Progressing to mCRPC
Pt was started on ADT with LHRH agonist-based therapy and abiraterone + prednisone. He also was placed on monthly zoledronic acid.
Patients is started on Docetaxel-based chemotherapy (75mg/m2 on 21-day cycles)
Patient completes 6 cycles of therapy with expected AEs including G1 fatigue, G1 alopecia and G1 peripheral neuropathy. His scans at the completion of chemotherapy showed SD with tumor burden reduction in liver lesions and SD in bones. His Hemoglobin level at the completion of chemotherapy is 12.1 g/dL and his ANC and platelets are also within normal limits.