Understanding Toxicities of Each CDK4/6 Inhibitor in HR+/HER2– mBC

From QTc prolongation to gastrointestinal (GI) toxicities, CDK4/6 inhibitors can present a number of adverse effects (AEs) for patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer, depending on the agent. In an interview with Oncology Nursing News, Kristi Orbaugh, MSN, RNP, AOCN, AOCNP, explained some of the key differences between palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio).

After moderating a Case-Based Roundtable, Orbaugh, a nurse practitioner at Community Hospital Oncology Physicians, in Indianapolis, Indiana, shared methods for monitoring for these AEs across treatment with each of the approved CDK4/6 inhibitors.

Oncology Nursing News: Which AEs are most prevalent in treatment with palbociclib?

Orbaugh: Palbociclib was the first [CDK4/6 inhibitor] on the market. It’s been out for about 10 years, so it was the first in class. When we’re talking about putting someone on palbociclib, the biggest toxicity we want to think about is neutropenia and making sure that we’re following their counts along. That’s important. We want to make sure that we’re getting baseline complete blood count and comprehensive metabolic panel—for all of these drugs, not just for palbociclib. With palbociclib, we’re checking every 2 weeks for the first 2 cycles and then monthly for the next 4, and then, as clinically indicated. It can be paired with an [aromatase inhibitor] or fulvestrant [Faslodex] in certain cases.

Which AEs should nurses and advanced practice providers monitor for with ribociclib?

Ribociclib has some hepatotoxicity, so we’re going to make sure that we’re watching those transaminases on a regular basis. Are they on any other medications that can cause issues with transaminases or liver function in general? We also know that there’s a risk of QTc prolongation, so with ribociclib, similar to palbociclib, we’re going to check counts because there is a risk of neutropenia.

We’re also going to do ECGs [electrocardiograms]. You need an ECG at the outset, 2 weeks later, a month later, and then as clinically indicated. If they have any history of atrial fibrillation or if they have any history of arrhythmias, that needs to be considered. Are they on any other medications that have the potential to cause QTc prolongation? Ondansetron (Zofran) is a drug that we use all the time in oncology. It certainly is the backbone of treating patients with nausea, and it can cause some QTc prolongation. My point in saying that is to make sure we know all the medications that they’re on, because you would need to know if they were on more that have the potential to increase that repolarization time period in the heart.

How do dosing schedules for CDK4/6 inhibitors factor into treatment decisions?

Ribociclib and palbociclib are on a 3-week-on, 1-week-off regimen. That, in itself, is important, especially if you have a patient who has some confusion. Especially if you have a patient who doesn’t have a lot of support, you want to make sure that you have a good plan in place to set them up for success. [They need to know] how to take that drug for 3 weeks, continue with their endocrine partner on the weeks that they’re off, and then start it back again at the start of a new cycle. That’s very important.

What toxicities present with abemaciclib?

With abemaciclib, we see less neutropenia and less bone marrow suppression, but we can see more GI toxicities. Abemaciclib is the only one that patients will take every single day. That does have its advantages, especially if you have a patient that doesn’t have a lot of support or has some memory issues. Not that the other 2 can’t be used; they certainly can. You just want to make sure you have a very simple plan in place.

You want to make sure that you’re talking to patients about having an antidiarrhea medication on hand. They need to know when to start it and how to maximize it. You’re going to want to make sure that you’re following up with them on a regular basis. Do they have any history of irritable bowel [syndrome]? Do they have a history of significant diarrhea already? Those are things you need to know when you’re choosing these medications.

How do you educate patients about GI toxicities before starting abemaciclib?

If I’m putting a patient on abemaciclib, I always remind them that the first month or so that you’re on abemaciclib is not the best time to try every fried food in the world. It’s not time to go to the state fair and eat from every single food truck. You want to use some good common sense. For example, if there are certain spices that historically have caused the patient to have an upset stomach, the day they start abemaciclib may not be the day that they [should] eat foods related to that.

How can you tell if a patient is having GI toxicities with abemaciclib?

Make sure you know patient’s baseline. Just like with neutropenia and liver functions, you need to know baseline. If you don’t know baseline, how are you going to react? When we’re talking about GI issues, we need to know: Is this a patient who goes [to the bathroom] every day? Is this a patient who goes every other day? Is this a patient who has softer stools at baseline? If a patient is someone who doesn’t always go to the bathroom every single day, and suddenly they’re going—there may not be watery stools, but they’re going 2 to 3 times a day—that’s something I want to know about.

This transcript has been edited for clarity and conciseness.

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