Case Studies: An 80-Year-Old Man, As Well As a 62-Year-Old Man, With Metastatic Castration-Sensitive Prostate Cancer - Episode 5
Dan Petrylak, MD, discusses the pros and cons of using abiraterone as a front-line therapy for mCSPC and provides details of the PEACE-1 study.
Dan Petrylak, MD: My feeling is that there's a relative contraindication of abiraterone in patients who have preexisting cardiac disease based upon the data that came out of Jefferson. I'm going to take a cardiac history very carefully. But, I think that abiraterone and prednisone is an appropriate treatment for patients with frontline therapy. Again, it's a matter of convenience and a matter of whether a patient wants steroid treatment or not. It is also selected based upon side effects. For this patient, it's appropriate to give abiraterone and prednisone because he does not have any cardiac history, no issues in terms of his liver function, and no issues in terms of hypertension.
If a patient had a rising PSA [Prostate-Specific Antigen], and if a patient had new symptoms such as bone pain or significant weight loss, then I would consider imaging the patient and determining whether they have resistant disease or progressive resistant disease. We also measure testosterone levels to be sure that they're castrated. At that point, I would consider changing therapy since this patient has been on abiraterone. If the patient is asymptomatic and he maintains a low volume of disease, in other words, his PSA is less than 22 as a first therapy, I would consider Provenge [Sipuleucel-T]. I would also consider docetaxel chemotherapy if the patient were rapidly progressing or if he developed visceral disease. Again, as I mentioned before, we talk about next-generation sequencing and looking at molecular markers. The 2 most important markers at progression to look for are DNA repair mutations, as well as microsatellite stability. For patients with BRCA1, BRCA2, as well as other DNA repair mutations, there are FDA [Food and Drug Administration]-approved drugs, such as olaparib, for patients who've been on prior abiraterone. Rucaparib is approved for those patients only BRCA1, BRCA2, and those patients who have had both docetaxel as well as a next generation to antiandrogen. Another thing we look for is microsatellite instability which marks for response to pembrolizumab. That overall is 3% of patients with castration-resistant prostate cancer. The therapy that we add will be dependent upon on the molecular profile and upon the disease state as well as the prior therapy.
There are really 4 adverse events that we worry about with abiraterone. 1 is hypertension, 2 is hyperemia, 3 is liver function abnormalities, and 4 is edema. The 2 most important are hypertension as well as liver function abnormalities. Hypertension, of course, is managed with medication. Often, I will co-manage a patient with an internal medicine physician. Liver function abnormalities usually get better if you stop the drug. The LFTs [liver function tests] will go back down again. In rare cases, we have given steroids when we've identified an autoimmune component to the patient's liver function abnormalities. They're managed with stopping the medication and steroids, if appropriate.
The PEACE-1 study randomized patients to the standard of care docetaxel or the standard of care docetaxel followed by abiraterone and prednisone. A significant improvement in overall survival was shown with the combination treatment overall over docetaxel by itself. This leads to a very interesting conundrum, which is: what is the role of abiraterone? Can we get away with giving abiraterone by itself? Or is the combination with the sequential treatment of abiraterone and docetaxel necessary? We really don't know the answer to that question because there was no control arm of abiraterone alone. What I think this has implications for in terms of patient care, is for any patient who goes on chemotherapy, I'm going to discuss whether they should go on abiraterone or not afterward. In fact, given this data, I would recommend that the patients do this because clearly, there is an improvement, but it doesn't tell us whether everybody should receive chemotherapy and then abiraterone afterward. I think that for those patients who receive chemotherapy upfront, they should receive abiraterone and prednisone. This data does not help us select between different treatments in either abiraterone, enzalutamide, apalutamide, or chemotherapy or sequential treatment in those situations.
This transcript has been edited for clarity.
Case 1: An 80-Year-Old Man With Metastatic Castration-Sensitive Prostate Cancer
Patient History, Lifestyle and Clinical workup
Case 2: A 62-Year-Old Man With Metastatic Castration-Sensitive Prostate Cancer
Patient History, Lifestyle and Clinical workup