Treatment options for high volume mCNPC
Raoul S. Concepcion, MD, FACS: For this patient, we presented it as a low volume disease. In survey question 4, if the patient had high volume disease â Jason, as you and Oliver pointed out, high volume disease is defined as visceral metastases or more than 4 bone metastases, 1 through exterior of the axial skeleton. Would this affect your choice of treatment? In other words, would you use abiraterone-ADT [androgen deprivation therapy], enzalutamide-ADT, docetaxel-ADT, apalutamide-ADT? Then would you add an antigen receptor targeting agent, enzalutamide-abiraterone plus docetaxel-ADT or whatever? Dan, when you see these de novo metastatic castration naÃ¯ve patients, does the volume of the disease play a role for you in relation to your treatment options?
Daniel P. Petrylak, MD: Yes, the volume of the disease, the age of the patient and the co-morbidities all play an important role. Recently, we had the PEACE1 trial, where patients received the gold standard docetaxel and then were randomized to receive the observation or abiraterone. There was a significant improvement in rPFS [radiographic progression-free survival] in patients who received the 2 different treatments, docetaxel and abiraterone. While we don’t have any abiraterone arms, which would have been wonderful for this study, it’s something I have to discuss with my patients. It is a complex course of action because the results have been so striking. It has to be administered. I will look at the age, the aggressiveness, the comorbidities. Abiraterone may not be an appropriate medicine for patients with pre-existing cardiovascular disease because it can cause hypertension. There have been reports from Lenny’s institution [Thomas Jefferson University at Sidney Kimmel Medical College], where there is an increased rate of cardiovascular morbidity in patients treated with abiraterone who have pre-existing heart problems. I am going to look at my patient in terms of long term goal, how long he is going to be treated, what his overall performance is and how much disease he is.
Oliver Sartor, MD: Dan, that’s very well said. I want to make a quick comment going back to Lenny. We have castration resistance data on taking 1 abiraterone with food versus 4 without food. There is also a Canadian trial which had 2 with food as opposed to 4 without. In each trial, each of which is relatively small, there does not appear to be a difference between 1 with food or 4 without food. There is no data sensitive to castration [disease], but for people with significant financial toxicity, you can reduce the price of the drug by 75% and see if you think abiraterone may be appropriate.
Dan raised a few good points. I don’t mean to disagree with Dan, but if you think abiraterone is appropriate and financial toxicity hits 4, you can go down to 1 or 2 abiraterone with food as a poor man’s substitute. It is not FDA approved, not really proven, but something that I have done in practice to deal with the problem.
Raoul S. Concepcion, MD, FACS: We went to basically standard dosing regardless of body weight and everything with all those oral agents. Oliver, you raise an interesting point. Has anyone considered potentially checking PK [pharmacokinetics], abiraterone or enzalutamide to see metabolism and bioavailability and that sort of thing with PSA [prostate-specific antigen] reply?
Daniel P. Petrylak, MD: It is doneâ¦. It was published in JCO [Journal of Clinical Oncology] a few years ago in a disease resistant to castration. I always bring up a very interesting point because we know that the PK of docetaxel is different if there is testosterone on board. If you want to avoid this, maybe you just wait. In most of these trials, if all of these trials administer abiraterone within 3 months of starting the initial androgen deprivation therapy, if testosterone reaches castration levels within a month, I don’t think that PK will make a big difference. . It will be pretty much the same. You can probably get away with it. If you want to formally assess this, you will need to do so at the time you castrate the patient, but it probably won’t be any different. This is a very interesting and important point.
Raoul S. Concepcion, MD, FACS: Do medical oncologists have experience with generic forms? Not necessarily for this patient, but in general, generic forms of abiraterone vs the Janssen product. Do you have any experience with this, whether using it or how expensive or inexpensive it could be?
Oliver Sartor, MD: The price is better. It is difficult to assess. I know you can go to the Costco drugstore and get some great bargains. It’s hard for me to approve anything beyond that because I can only talk about the price. I cannot speak of efficiency.
Daniel P. Petrylak, MD: There is the new Kirkland abiraterone. This is a very interesting point. I haven’t seen much of a price difference with the generic in my experience. It may be regional and insurance dependent, but I didn’t see much of a difference.
Jason M. Hafron, MD, CMO: To develop this, the problem with generics is that you can’t get basic support. Sometimes it works against you if you can’t get that base support for a credits roll. Sometimes it’s counterintuitive, but it’s more difficult to write for the credits.
Raoul S. Concepcion, MD, FACS: Jason, do we know there’s another brand name drug, microparticulate abiraterone? Do you have any experience with this?
Jason M. Hafron, MD, CMO: It’s limited. We are testing a granule that you can put in a liquid. But for the 1 you are referring to, the data is limited; not a great experience. I want to go back to PEACE1, however. Dan mentioned PEACE1. I’m just a community urologist treating patients, and I’d like to hear the panel’s response. When I saw this data I was blown away by the rPFS [radiographic progression-free survival] and operating system [overall survival] from ESMO [European Society for Medical Oncology], and that was really impressive because this is the first major trial since 2015. Prior to that, the median survival was 3 years. When you look at the data, the median survival is over 5 years. In my book, it was a game-changer in how to handle this high volume patient with mCSPC [castration-resistant prostate cancer]. I’m curious if you see it that way, or if you still have questions about it?
Oliver Sartor, MD:Some problems. # 1, the proper control should have been ADT-abiraterone as we don’t know if docetaxel adds value. # 2, and one of the reasons I didn’t mention PEACE1, is that the high volume subset was the only one that benefited from it. If you look at the presentation of Grain, the low volume subset had no survival benefit. Now rPFS was better, but we are not treating people for our PFS [progression-free survival] in general. We want that benefit from SG, and it was high volume funding limited to disease.
Daniel P. Petrylak, MD: This was what I wanted to say before, and it helps us answer the question when a patient comes to the clinic and says, “Doc, I want the kitchen sink thrown out at me.” I want it all done. I want everything up front. For low volume patients, there is no major justification for this. For high volume there is.
Raoul S. Concepcion, MD, FACS: Lenny, I’ll give you the last word. Dan made a few comments when discussing the comorbidities of the patients he was examining. He mentioned the cardiovascular dysfunction that can be associated with abiraterone. We haven’t talked about it – it’s not really part of it – but when you see a patient’s cardiovascular history, how hard are you trying to determine whether to use an LHRH? [luteinizing hormone-releasing hormone] oral agonist or antagonist?
Leonard G. Gomella, MD, FACS: It is certainly an ongoing debate. Our mantra at the multidisciplinary Kimmel Cancer Center is that even if you have a urologist or GU [genitourinary] a medical oncologist takes care of you, you need a primary care physician to organize your overall health. We rely on this primary care physician to make sure we have good cardiovascular health. Dan mentioned high blood pressure and other problems with abiraterone. So we make sure the patients have a good doctor from head to toe, and we make sure we co-manage the patients because I can’t assess how big or how insignificant a person’s cardiovascular disease can be. We are coming to that phase right now, where men are living longer and longer. These problems will become more important as men spend many years working with these agents. We don’t know what the long term impact is. We don’t use a lot of oral agent. At Jefferson, we have limited experience in this area as we often encounter insurance issues in the Philadelphia market with an oral agent. Injectables we never have a problem with, but these are all things we need to look at: quality of life and quantity of life. With all these options, we will have more weight to personalize the treatment of a patient according to all the aspects of his life: financial toxicity, comorbidities, their expectations. We throw the kitchen sink at people. Some want that. Others say, âI’m fine. I have my 18 great-grandchildren. I don’t need all of that. It must be very personalized.
Raoul S. Concepcion, MD, FACS: Very nicely said, Lenny. A good point to remember to conclude that it is toxicity. We’ve always thought of toxicity as a big physiological factor, but Dave Penson gave a good talk a few years ago about how we should view financial toxicity in the age of multiple drugs and the cost associated with agents. targeted.
Transcription edited for clarity