Management of Adverse Events in M0 CRPC

Transcript: Judd Moul, MD: The issue is an important teaching point. It segues into a brief discussion on adverse effects. Tanya, you mentioned that apalutamide has the unique adverse effect of rash. In the trial, about 24% of patients in the SPARTAN trial had some degree of rash, but only 5% of the time it was a grade 3 or 4. The vast majority of those patients can be managed with a brief drug holiday. Less than 10% of patients actually required systemic steroids to treat the rash. For the most part, it’s fairly manageable.

To both of your points about measuring thyroid function, in the SPARTAN trial, apalutamide—if I’m not mistaken—had about an 8% risk of some abnormality in the TSH [thyroid-stimulating hormone] or thyroid levels. The FDA does not require any monitoring. Rightly or wrongly, as a urologist, I have not ordered any thyroid testing on patients who are on apalutamide, and that is following the label. You certainly can’t be criticized for ordering a thyroid function test, but these guys are all on Lupron, or LHRH [luteinizing-hormone releasing hormone] or GnRH [gonadotropin-releasing hormone] agents. They’re all going to have some fatigue. How do you know? What was your rationale for ordering? Did you order it regularly just as a routine?

Alicia Morgans, MD, MPH: I do, because I would want to supplement it if they had hypothyroidism. I’m only ordering a TSH [thyroid-stimulating hormone] test with a reflex-free T3 and T4. I’m ordering a TSH test, and then only if that’s abnormal do I look into the T3 and T4. I’d make my decisions about whether someone has hypothyroidism based on the T3 and T4, not just the TSH. A lot of these guys have complex medical situations, and you can have subclinical hypothyroidism that’s just a TSH being elevated, which is not something that I would ever want to treat.

In busy urology practices, this is not something that I’ve done for any other medication in a very long time. Urologists are not used to ordering medications to supplement thyroid. This is something that could potentially be done twice a year, in a partnership with a primary care doctor, with some of the midlevel tests that practices have to monitor bone health and to continue with the LHRH agonist/antagonist visits that urology practices sometimes have a midlevel doing. This doesn’t necessarily have to be done by a urologist, but I would check in at least annually or even twice a year with a TSH test. This is something that can make your patients feel pretty crummy, and you can fix it.

Judd Moul, MD: Again, playing devil’s advocate, more than 90% of the patients didn’t have problems, so you are adding cost to care for something that 90% of the patients did not develop. Your point is well taken. The key teaching point is that listeners have to be aware that apalutamide has a risk of thyroid abnormalities, and it occurred in about less than 10% of the patients, but they need to be aware of that.

Neeraj Agarwal, MD: I would like to make a point. The fact that we are talking about thyroid dysfunction in these patients tells us how well tolerated these drugs are. That’s the bigger message I’m gleaning from our discussion right now. We are not talking about neutropenia. We are not talking about infections or colitis. We are not talking about those severe adverse effects, which have remained at the center of all discussions around all anticancer therapies. This is a great news, overall, right?

Judd Moul, MD: I agree.

Neeraj Agarwal, MD: The second thing I want to mention is the rash. We didn’t discuss that. In my practice most of the rashes have been self-limiting. Patients rarely require systemic corticosteroids. I don’t think I’ve ever used systemic corticosteroids for these patients. If somebody has rash—a grade 1 or 2—I usually tell them to wait it out and get some Benadryl, and most of these patients feel better. If the rash goes beyond grade 2 to grade 3 or 4 and starts really bothering patients, local topical corticosteroids are usually enough to treat these self-limiting rashes.

Beyond that, I think we don’t have to really worry about any adverse effects beyond making sure that patients are being monitored for bone health. As Alicia, who’s a leader in this field, very rightly pointed out, it’s important to make sure bone health is maintained. Patients must have a good primary care doctor if they are being managed by a urologist, but I think that’s it. We don’t really have to worry about too many adverse effects.

Judd Moul, MD: To follow up on the apalutamide, I’ve had 1 patient who’s had a rash. When I talked to him on the phone, he said he was like a Dalmatian dog, but instead of having the black spots, they were red. They didn’t itch. We managed that with a drug. I worked with the oncologic pharmacy professional at my institution, and as a team, we decided to give him a drug holiday for about 2 weeks and then reintroduce it at three-quarters of the original dose, and there were no more problems. I did not treat him with systemic steroids. I did not treat him with topical steroids. But on someone’s suggestion, I told him to use some Eucerin cream or a similar product.

Neeraj Agarwal, MD: I agree with you, Judd. Most of these patients will respond by dose reduction or temporary discontinuation. We don’t need steroids, but for 1 of those rare patients who has grade 3 rashes that really bother them, I think it’s fine to use some topical steroids.

Judd Moul, MD: Correct.

Neeraj Agarwal, MD: Benadryl or other simple drugs are also suitable. I don’t think we have ever used systemic corticosteroids. That is the point I was trying to make.

Judd Moul, MD: In the trial, I think it was 5% who had grade 3 or 4 rash, and maybe 4% of patients required systemic steroids. It was a fairly low amount.

Transcript Edited for Clarity