Nicholas Vogelzang, MD: Hi, I’m Nick Vogelzang, a medical oncologist in Las Vegas, Nevada.
Daniel Petrylak, MD: Hi, I’m Dan Petrylak, a medical oncologist, Yale University, New Haven, Connecticut.
Nicholas Vogelzang, MD: We’re here today to talk about the changing landscape of castrate-resistant and hormone-sensitive metastatic prostate cancer. Dan and I have both had the opportunity to be in this business for a full 30 or 40 years, and we’ve seen a lot of changes. The changes we’re seeing are continuous, and I’d like to spend a little time going over some of those changing landscape issues that Dan and I both have enjoyed watching and sometimes leading. Dan, what do you see as the biggest change in the last say 5 years or so?
Daniel Petrylak, MD: I think the biggest change is the earlier use of agents that we had traditionally used in castrate-resistant prostate cancer, moving these agents up to the hormone-sensitive state. And we’ve seen a tremendous increase in the overall survival of men with metastatic prostate cancer by the early use of these agents.
Nicholas Vogelzang, MD: What do you think about the use of docetaxel earlier? Is it catching on or is it not catching on?
Daniel Petrylak, MD: I think it’s had a wave. It’s had 2 different waves of popularity so to speak. When it was first introduced by Chris Sweeney, MBBS, in the CHAARTED trial, we saw about an 18-month improvement in median survival for those patients who had high-risk disease, and 6 cycles of docetaxel without prednisone, and you were basically finished with your treatment.
Then with the introduction of abiraterone and prednisone in the same space, also now with enzalutamide, as well as apalutamide. We have other competing drugs, each of which have their own advantages and disadvantages; we’re seeing less of a use of docetaxel in this particular space.
Nicholas Vogelzang, MD: I heard an interesting statistic the other day that only about 5% of patients in the United States are getting docetaxel in the hormone-sensitive state. Do you have a theory or a hypothesis as to why that is?
Daniel Petrylak, MD: I think there are several reasons. There’s always this stigma that goes on with chemotherapy that it’s toxic, and you have to go to the doctor’s office to get an infusion as opposed to getting an oral pill with abiraterone or enzalutamide or apalutamide.
Nicholas Vogelzang, MD: Well, I know I’m personally still using a lot of docetaxel, and I find that if you approach the patient right when they’re diagnosed, they’re not so negative about it, because they’re frightened. More importantly, you say, “Look, then I’ve got all these androgen receptor inhibitors that I could use after the docetaxel.” How do you use it in your practice?
Daniel Petrylak, MD: I have a discussion about the short-term and the long-term adverse effects of these particular agents. Particularly with docetaxel we know that you can get some neuropathy and neutropenia. When you do the 6 cycles of treatment, you’re done—it’s over with, you don’t have to worry about taking a pill. We know that abiraterone and prednisone do have some cardiovascular effects. In fact, from Thomas Jefferson University last year there was a report that there was a high rate of cardiovascular events in patients with pre-existing cardiovascular events. For a patient who has cardiac dysfunction, I’m going to lean away from giving abiraterone and prednisone, and perhaps docetaxel, apalutamide, or enzalutamide.
Nicholas Vogelzang, MD: Have you used a lot of the enzalutamide up front in the hormone-sensitive space?
Daniel Petrylak, MD: I’ve used it to some degree, not a lot but to some degree.
Nicholas Vogelzang, MD: Yes. I’ve shied away from it because of the CNS [central nervous system] toxicities, and I’ve been a little reluctant to push really hard, particularly because these guys often are older.
Daniel Petrylak, MD: I agree with that, and I think that one of the drawbacks to these agents, and we have underappreciated this, are the long-term effects on muscle mass, on mental function. I’m seeing patients having more and more fatigue on a chronic basis as they’re getting out to 2 years on abiraterone. This I think is something we have to be very careful of. Remember in the castrate-resistant state, you’re only giving these drugs for a shorter course of time. Over a longer course of time you may see other adverse effects that may impact significantly on quality of life.
Nicholas Vogelzang, MD: In this changing landscape where do you think the PARP [poly ADP ribose polymerase] inhibitors will go in the earlier hormone-sensitive phase?
Daniel Petrylak, MD: Well, I think it’s certainly something we need to do on a trial basis. We don’t have any evidence at this point of using PARPs in the BRCA-positives in hormone-sensitive disease. Again, we’ve got to think about the long-term side effects, including the effect on the bone marrow, because anemia and thrombocytopenia are significant adverse effects with the PARP inhibitors. But I think at the same time we have active agents. Perhaps we need to give these in short courses, like docetaxel. There are trials that are being designed to look at that particular question.
Nicholas Vogelzang, MD: I think they are going to be potentially useful in that space, but I’m not sure yet. They’re fairly difficult on the bone marrow.
Daniel Petrylak, MD: Exactly.
Nicholas Vogelzang, MD: I’m not sure where we’re going to go with that.
Transcript Edited for Clarity