The Efficacy and Safety of CDK4/6 Inhibitors


A comparative evaluation of the safety and efficacy of 3 cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors: ribociclib, palbociclib, and abemaciclib.


Joyce O’Shaughnessy, MD: Abemaciclib does have diarrhea toxicity that is not seen, generally speaking, with palbociclib and ribociclib. Of course, it has less myelosuppression. If patients have issues with bone marrow then it’s obviously a good option for them. But abemaciclib, because of the every-day dosing schedule, may have a greater role to play in more aggressive disease. There are some subset analyses that suggest liver metastasis and a short disease-free interval, where patients haven’t had the most endocrine therapy-sensitive type of disease, like with palbociclib in the PALOMA-3 trial, and the real benefit in survival with those who did have more endocrine therapy-sensitive disease. So that’s a question that’s still kind of emerging.

But with the daily dosing and not needing to take the week off, if you’ve got aggressive disease in the liver that’s really pretty explosive, then it may make some sense, although we don’t have head-to-head comparisons. But that’s where I do utilize it. I find that it really is important for the woman to manage the diarrhea over the first month or 2. After that, it really does tend to settle down. They may experience it 2 or 3 times a week and may need to use Imodium [loperamide].

I find that women kind of figure out how to self-modulate on the diet. They tend to eat smaller meals more frequently. They don’t eat too much at 1 time. They don’t eat heavy, rich foods that can cause more diarrhea. So the women just start eating a bit more lightly and a little bit more frequently. Interestingly, they manage the diarrhea a lot by diet in the first month or 2, with some Imodium on top of things. But we give the patients so much information when they come to the clinic.

Michael Reff, RPh, MBA: Yes.

Joyce O’Shaughnessy, MD: We’ve got the bad news of, “You know, the cancer is progressing.” And we’ve got the bad news of, “We’ve got to change therapies. Here is the list of options. Let’s talk about the options.” “Here’s what I think is best for you. Here’s how you take it. Here are the adverse effects.” It’s a lot of information.

Michael Reff, RPh, MBA: What you just described to me emphasizes the importance of having a medically integrated team. And to help describe that even further, you painted that picture very well.

Regarding NCODA [National Community Oncology Dispensing Association], not only is there a teaching consent from the prescribers: “This patient is going to be on this therapy. Here are some clinical benefits that we hope to expect. Here are some adverse effects that you may be experiencing.” But the oral oncology nurse down in the pharmacy or the pharmacist down in that space reiterates that same clinical message when they meet with that patient. This doesn’t just happen during the first time, but on subsequent refills as well.

And so, there’s consistency in that message, and education, which is critical. It’s important that individuals in the medically integrated pharmacy understand the importance of the nuances of these compounds. You mentioned diarrhea. “Guess what? It’s probably going to happen. And guess what? It will probably go away.” “We need to get you through this window, and here’s the window.” And it’s great that they’ve heard it, but you mentioned that patients are overwhelmed.

If they come down to the pharmacy and pick up their prescription and hear it yet again from a pharmacist or a nurse, and then receive subsequent follow-up calls from the nurse…. “Hey, you’re on day 3, how are you doing? These are some of the things you should be expecting. Are you taking this to help you with that?” These are the things that a medically integrated team does versus just filling a prescription for the sake of filling a prescription.

Joyce O’Shaughnessy, MD: Yes. That’s so good because if people haven’t really heard that and they’re not prepared, either they’ll stop taking the drug because it’s too much, or they won’t stop and will tough it out. They won’t call. Then you’ve got real problems. You’ve got real toxicities. You’ve got emergency department visits on your hands, hospitalizations, etcetera.

Michael Reff, RPh, MBA: Exactly.

Joyce O’Shaughnessy, MD: Which can obviously happen with significant myelosuppression, or diarrhea. So the medically integrated pharmacy team maintains a list of everybody they’ve prescribed these to. There is a lot of a coordination here, right?

Michael Reff, RPh, MBA: Exactly. Coordination is a great word for that, and that’s what I think we pride ourselves on. What I say to the NCODA members is, “We’re not here just to fill prescriptions, we’re here to do more than that. If your job is to fill prescriptions, there are other entities that do that. That’s not us. What we’re here to do is take it to the next level by being a part of that care team.” We get engaged specifically in the EMR [electronic medical record]. The EMR is critical, not only for the pharmacy team to understand the patient who they’re going to be seeing or helping, but also for communicating back to the prescriber that, “Hey, I just made a follow-up call and they’re starting to experience this.” Or, “I think we may have some issue with adherence. This patient may not be a good patient for oral therapy because they’re not really good with oral therapies.” If adherence is a problem, maybe an IV [intravenous] therapy would be preferable even though it’s not as convenient.

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