Safety Considerations in mCSPC and Selection of Androgen Receptor Pathway Inhibitors

Dr. Atish Choudhury discusses safety features to keep in mind when choosing androgen receptor pathway inhibitors.

Atish Choudhury, MD, PhD: So, the question is around the relative safety of the different agents, and so obviously we have a lot of data on all of these agents, and so docetaxel, for example, has a variety of chemotherapy-related side effects and complications that I think the audience here is pretty well aware of. One little pearl is that it’s important not to start docetaxel immediately at the onset of androgen deprivation, because chemical castration, the testosterone suppression actually changes the pharmacokinetics of the agent, and that effect takes several weeks to come into play.

The rate of febrile neutropenia is actually higher if you start docetaxel too early in the process, so I do recommend waiting about four weeks or so before starting on docetaxel. And docetaxel toxicities can usually be managed by dose reductions or dose delays whenever needed. When we’re talking about the other agents, which are abiraterone, enzalutamide, and apalutamide, again, they’re generally quite well tolerated with class-specific adverse events related to each agent.

Abiraterone is more likely to cause troubles with hypertension and cardiovascular issues, and enzalutamide and apalutamide are more likely to cause troubles with fatigue, a little bit of cognitive delay, maybe a bit of decrease in balance and increased risk of falls. So, how to pick a particular agent for an individual patient, it really depends on their comorbidities, and again, what the cost of these agents is really going to be.

Abiraterone is given with prednisone, so patients with poorly controlled diabetes or poorly controlled hypertension, that might be the less-favored agent, though I think in patients with reasonably well-controlled hypertension and diabetes, that abiraterone and prednisone is actually quite safe. For patients with rhythm issues that are not well controlled, I think that’s something that would need to be discussed with their cardiologist around whether abiraterone is safe, but in somebody with well-controlled atrial fibrillation, for example, abiraterone can be given and tolerated well.

With enzalutamide and apalutamide, I do have a little bit of caution in very elderly patients because of the higher risk of falls in that particular population, though I think starting both agents at a dose reduction might be a safe way to manage, and particularly elderly and frail patients. With apalutamide one needs to monitor thyroid function and needs to monitor for a rash, but the rashes are generally easily controlled with medication and dose reduction.

It’s something to monitor but shouldn’t generally be an absolute contraindication. So, a lot of what comes into effect also is just the oncologist’s familiarity with all of these agents, their familiarity with side effect management, cost of the medication, and drug interactions, but really all of them are very appropriate to use in the first line.

Transcript edited for clarity.

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