Safety Considerations in mCSPC and Selection of Androgen Receptor Pathway Inhibitors

Atish Choudhury, MD, PhD: So the question revolves around the relative safety of 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 side effects and chemotherapy-related complications that I think the public here is pretty well aware of that. A small bead is that it is important not to start docetaxel immediately at the onset of androgen deprivation, because chemical castration, suppression of testosterone, actually changes the pharmacokinetics of the agent, and this effect takes several weeks to appear.

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

Abiraterone is more likely to cause high blood pressure and cardiovascular issues, and enzalutamide and apalutamide are more likely to cause fatigue issues, mild cognitive delay, possibly mild loss of balance and an increased risk of falls. So how to choose a particular agent for an individual patient really depends on their comorbidities, and again, the actual cost of those agents.

Abiraterone is given with prednisone, so patients with poorly controlled diabetes or poorly controlled hypertension, this might be the least favored agent, although I think in patients with hypertension and diabetes reasonably well controlled, abiraterone and prednisone are actually quite safe. For patients with rhythm issues that aren’t well controlled, I think that’s something that should be discussed with their cardiologist to see if abiraterone is safe, but in someone with atrial fibrillation well controlled, for example, abiraterone can be administered and well tolerated.

With enzalutamide and apalutamide I exercise some caution in very elderly patients due to the higher risk of falls in this particular population, although I think starting both agents at a reduced dose might be a safe way to manage, especially the elderly and frail patients. With apalutamide, thyroid function should be monitored and rash monitored, but rashes are usually easily controlled with medication and dose reduction.

It is something to watch out for but generally should not be an absolute contraindication. So a lot of what comes into effect is just the oncologist’s familiarity with all of these agents, their familiarity with side effect management, drug cost and drug interactions, but in reality they are all very suitable to use in the first line.

Transcript edited for clarity.

Martin E. Berry