Advances in the Treatment of Prostate Cancer - Episode 4

Benefits of Newly Approved Drugs for M0 CRPC

Transcript: Judd Moul, MD: In February of 2018, we had apalutamide. That was the first one available for nonmetastatic CRPC [castration-resistant prostate cancer], and then about 6 months later, we had enzalutamide. Over the past year or so, we’ve had both of these agents available. How do you make a distinction, or how do you decide in your own practices which agent to use? That’s a tough question. Neeraj, can you address that?

Neeraj Agarwal, MD: Yeah. In general, given that there is so much similarity between the data sets so far, the choice is driven by how easily the drug is available to our patients. I think that’s the number 1 criteria for all of us. How easy, or how good, is the copay assistance program? That is driving, and will continue to drive, the uses of these drugs until we see the final overall survival data. If a drug is better than another drug from an overall survival perspective, then it will become more evidence-based and you can compare to determine which is better. So far, all of these 3 drugs seem to be very similar in the M0 [nonmetastatic] CRPC setting, and seem to benefit patients. Of course, they have not been compared with each other in a randomized fashion, so I will never compare these drugs until we have those data. To me, enzalutamide, apalutamide, and darolutamide seem to be benefitting patients by delaying skeletal-related events, improving pain scores, and so on. Ultimately, the number 1 factor is how easy it is for my patients to get these agents.

Judd Moul, MD: Tanya, did you want to make a further comment on that?

Tanya Dorff, MD: I would say that the darolutamide data do seem to indicate smaller differences in some of the toxicities that my patients complain about the most when they are on 1 of these agents, compared to placebo, which include things like fatigue or cognitive changes. I think falls were also more similar between darolutamide and placebo, compared to the differences between enzalutamide and placebo or apalutamide and placebo. The chemical structure is a little bit different. I completely agree that access and formularies will drive some of our prescribing practices. If you think about what your patients call in for, when you need to dose reduce, and discontinuation rates, all of those things give you a sense of how much bother the agent is giving your patient. I think it’s possible that there will be a little better tolerability with the darolutamide. I don’t know how you feel about that.

Judd Moul, MD: It’s interesting. I haven’t had access. None of us have access to darolutamide yet, outside of the research study, because it’s not FDA approved. In my experience with enzalutamide and apalutamide as a urologist, I would make the point that these are fairly straightforward drugs. They’re not the oral agents for kidney cancer or some of the more toxic agents that medical oncologists use every day. I want to make a point that urologists certainly should not be scared away by using these agents. We urologists grew up with BCG [Bacillus Calmette-Guérin] to treat bladder cancer, and I get a lot fewer callbacks and issues from patients being treated with enzalutamide or apalutamide than when I was doing bladder cancer with BCG.

Tanya Dorff, MD: The majority of patients tolerate any of these agents well. I will challenge you a little bit about the simplicity of these agents, because if we’re going to maintain our patients’ quality of life, they’re going to be on lifelong testosterone suppression, and we do need to be very vigilant about counseling them on exercise and diet to stay healthy. We need to make sure we’re watching their bone density and supporting their bones so they don’t end up with an osteoporotic fracture, which will significantly diminish their quality of life. They are deceptively simple in that we don’t need to monitor a lot of things day in and day out, but we also need to make sure we’re taking good care of our patients for the long-term.

Judd Moul, MD: Excellent point.

Neeraj Agarwal, MD: I have 1 quick point on this. Whenever anyone prescribes these agents, it’s very important to know that they have significant drug interactions with many other agents. I agree with you; we don’t have to monitor for liver function tests or electrolyte imbalances. We are not dealing with the neutropenias we used to or currently see with chemotherapy agents, but there has to be somebody on board keeping an eye on the drug interactions. These patients are older patients. They have comorbidities. They are on drugs for lowering cholesterol, hypertension, or heart diseases. The levels of all of those drugs can go up or down depending upon which one of these drugs we are using. I think it’s very important to get primary care doctors or pharmacists involved. In your practice, if you don’t have access to the primary care doctors, make sure somebody is keeping an eye on the drug interactions

Transcript Edited for Clarity