Kevin Kalinsky, MD, MS: We participated in the early study, and I remember, in the back of my head, when the drug was being developed, the reiteration was, “You should let the patients know that this is an adverse effect.” That’s always kind of stuck with me. Whenever we prescribe abemaciclib, we say, “This is the adverse effect to look out for. Give us a call on the first sign of diarrhea. When you order the medicine, you can get the Imodium kit.” So we make sure they have that at home. And then, if patients develop more than grade 1 diarrhea, if it’s a grade 2 diarrhea, they hold the medication. And if it goes down to grade 1, they can resume at that same dose. But if it’s a recurrent issue, then they dose reduce. But I tend to, especially with the 150-mg dose, if you’re giving it along with hormonal therapy, it tends to be manageable.

Joyce O’Shaughnessy, MD: And you find that the dose reduction, in those patients who need to, does help?

Kevin Kalinsky, MD, MS: Yes.

Joyce O’Shaughnessy, MD: It does reduce the diarrhea?

Kevin Kalinsky, MD, MS: Yes.

Joyce O’Shaughnessy, MD: How about you, Hope? What’s your experience been so far?

Hope S. Rugo, MD: It’s so interesting, having enrolled patients first in MONARCH 1. We gave a higher dose as a single agent—these were heavily pretreated patients—and we did see some diarrhea. They would hold the drug or would give themselves Imodium or wouldn’t eat the spicy foods, right? I remember one of my patients was always carrying Imodium in her purse so that she would have it just in case. But then, when you use the lower dose with hormone therapy, we just stopped seeing a lot of diarrhea. It’s not of high grade. They get some loose stools, but generally manage it pretty well with Imodium. I think one of the hardest things for some people is just figuring out which dietary things may set them off, and we see that with other medications as well, even pertuzumab, actually. So I haven’t had a lot of problems with diarrhea. And, again, maybe it’s a patient population issue.

Joyce O’Shaughnessy, MD: How about you, Ruth?

Ruth O'Regan, MD: No. I agree with Kevin’s management. It hasn’t been as huge of a problem as maybe we would have expected.

Joyce O’Shaughnessy, MD: Yes. My patients have all modified their diet. First of all, it seems to be 4 to 6 weeks anyway. For a few patients, I did have to dose reduce. It was more like 2 or 3, for whom I did have to dose reduce. But everybody else basically says, “I have 1 or 2 loose stools a week.” That is what they usually say, and they just take loperamide.

Hope S. Rugo, MD: That’s a great one, yes.

Joyce O’Shaughnessy, MD: A lot of the ladies will modify their diet. As you said, some patients will just stay away from the heavy, spicy foods or just eat smaller amounts. One woman told me yesterday that if she eats a big salad, you know, big fiber, she’ll have a loose stool. But it’s really quite manageable, and they can pinpoint what it is. So it is something that seems to be kind of a nonissue for most patients, you know? Any other toxicities that you guys have run into? Anything else?

Ruth O'Regan, MD: Fatigue is sometimes an issue.

Kevin Kalinsky, MD, MS: Yes.

Ruth O'Regan, MD: I certainly had a patient come off because she’s got really bad fatigue now, and she had chemotherapy and radiation. But it seems to be related, so that’s one other thing that I’ve seen. But apart from that, I think they’re well-tolerated.

Kevin Kalinsky, MD, MS: Yes. The other adverse effect that I now preemptively talk to patients about is alopecia. I do, just because I had 1 patient who experienced it. It’s not like what we see with chemotherapy. But I had 1 patient who was upset by the fact that she was having some hair thinning. So at that rate, across all of the different CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors, it is slightly higher. So I do mention that to patients.

Joyce O’Shaughnessy, MD: And pretty much across the board, do you think?

Hope S. Rugo, MD: About one-third of the patients, but mostly it’s grade 1. So it’s hair thinning. But I did have 1 patient who had a kidney issue. She had renal insufficiency and her hair fell out. That’s my 1 patient. So you can see why. It’s occasional grade 2 alopecia. I also tell everybody, because that’s one of the things that people really get mad about if you don’t warn them. But the fatigue issue that Ruth mentioned: I’ve found that to be a bigger issue in older patients in the metastatic setting. And yes, in the adjuvant setting it’s an issue for patients as well, regardless of age.

But for the older patients, we have dose reduced for fatigue. The FDA analysis of older patients found that they had more fatigue than younger women. So I think that fatigue is a real issue. We use methylphenidate for those patients, sometimes. But dose reducing and changing the schedule again…. There’s 1 woman who’s been on it now for several years, a CDK4/6 inhibitor, for whom we actually changed to 2 weeks on, 1 week off at 75 [mg] because she keeps getting so tired. She found that it was a huge quality of life issue.

Joyce O’Shaughnessy, MD: Yes.

Hope S. Rugo, MD: I think she might be age 81 now.

Joyce O’Shaughnessy, MD: That’s where I’ve seen it too. I’ve seen it with the older women, who have required a dose reduction. But it seems to help, you know?

Kevin Kalinsky, MD, MS: Yes.

Joyce O’Shaughnessy, MD: It’s generally manageable.

Kevin Kalinsky, MD, MS: But I do think that it’s an important point. Even if you look at the PALLET data, the randomized neoadjuvant study, there was a small percentage, about 4%, who had grade 3 or higher fatigue, right? So when we’re rolling these out into the operable setting, the allowance for that sort of adverse effect—we’ll see how many patients end up coming off in the operable setting.

Joyce O’Shaughnessy, MD: Yes.

Ruth O'Regan, MD: Really good point.

Joyce O’Shaughnessy, MD: Yes.

Transcript Edited for Clarity