CDK4/6 Inhibitors: How to Tailor Treatment Choices by AEs

Due to the unique safety profiles of abemaciclib, ribociclib, and palbociclib, treatment with CDK4/6 inhibitors can be tailored to a patient's needs.

CDK4/6 inhibitors remain a recommended frontline treatment for patients with hormone receptor (HR)–positive breast cancer; however, not every patient has the same history going into treatment. For this reason, the availability of several CDk4/6 inhibitors approved for the first line of therapy for those patients allows providers to create more individualized treatment, according to nurse practitioners Kimberly Podsada, BSN, RN, MSN, NP-C, CNS, and Courtney Moore, APRN, FNP-C, OCN.

Moore and Podsada, both of whom moderated Case-Based Roundtable discussions with peer advanced practice providers (APPs), explained how the adverse effects (AEs) associated with palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) can vary from one another. Notably, they shared methods for assessing which treatment is best for each individual patient.

Oncology Nursing News: What is the current landscape of treatment with CDK4/6 inhibitors?

Podsada: We have the luxury now of having a variety of CDK4/6 inhibitors to choose from, and we can tailor our choice based on the patient’s comorbidities, lifestyle obstacles, and preferences. We can look at the whole picture of the patient. How are their kidneys functioning? How is their liver functioning? What sort of support services do they have? Are they going to be able to get to clinic?

[We have] our first-line CDK4/6 inhibitors, and all 3 have demonstrated improvements in that setting. Yet there is provider preference, and now we can look at the individual as well and make that decision based on them and their preferences.

How do adverse effects differ across CDK4/6 inhibitors?

Moore: With palbociclib and ribociclib, one of the biggest AEs is neutropenia. We really monitor our patients’ CBCs. They need to come in every 2 weeks for the first couple of cycles, and then we will watch it monthly after that for ribociclib.

Another thing is the QTc. We’re going to be doing EKGs at baseline, and then 2 weeks after they start the medication, and as needed from there, there is also concern for hepatic toxicities, especially with ribociclib, so we will be checking their complete metabolic panel throughout the process as well, to make sure we’re not seeing an uptick in any of the liver enzymes. Then, generally, these medications can cause some fatigue. Abemaciclib can cause diarrhea.

How should a patient’s baseline preferences issues be assessed?

Podsada: One of the things I like to assess about my patients are the baseline issues that they’re already bringing into clinic: “I already have a sensitive gut.” “Oh, I had really bad nausea with pregnancy.” “I’m already on immunosuppressant for my rheumatoid arthritis.” I would be looking at all these things and making a decision.

If someone’s coming off of chemotherapy, and they still have [gastrointestinal] issues and they were never able to get on top of their diarrhea, am I going to prescribe abemaciclib? I don’t know. But if someone is already neutropenic because of previous therapies or other medications, am I going to prescribe [palbociclib] or [ribociclib] because of the risk of neutropenia?

It’s a very detailed conversation with the individual and looking at the whole person honestly and thinking about that—not just having your personal preference of, “This is the drug I always want to prescribe,” but looking at the patient and going, “How is this medication going to impact my patient’s quality of life and ability to get the best care I want to give her or him?”

How should CDK4/6 inhibitor treatment be personalized for patients with comorbidities?

Moore: The risk factors tie into the AE profiles of these medications. Between the CDK4/6 inhibitors, there are a couple that lean more toward neutropenia as a major AE, and we want to be aware of whether the patient is on any immunosuppressive therapies or has any other rheumatologic disorders or autoimmune disorders so that we can keep a close eye on them.

Ribociclib has the potential to cause some cardiology AEs. If we have patients who already have arrhythmias such as atrial fibrillation, we want to avoid ribociclib because it can prolong the QTc interval. Being aware of your patient and what other comorbidities they may have is important when you’re making that decision.

What other factors should be considered when determining the first line of therapy for a patient with HR-positive breast cancer?

Podsada: Some of [the participants of the discussion] were also in more rural communities. It’s like, “How are we going to get someone’s labs done? How are we going to get an EKG done? How are we going to get them back for visits, incorporating video visits or using a lot of the prompts or reminders to call the patient to check on them? Do you know that you have your labs?” It seems to take a lot of handholding up front, and then things get better, which has always been my practice.

If you’re giving a lot of attention and focus on [AEs] early on, patients like that support, and then they get into the rhythm and the routine of things, and they don’t need as much help, they just need to get over that hump of also learning the drug and the [AEs] that they have.

This transcript has been edited for clarity and conciseness.