Differentiating Between Adverse Event Profiles of Various CDK4/6 Inhibitors


Adverse event profiles of several approved CDK4/6 inhibitors are discussed.

Ryan Haumschild, PharmD, MS, MBA: We’ve talked about this already a decent amount throughout the conversation because so much of the conversation is centered around quality of life, efficacy, duration of treatment. But the [adverse] effect profile management is so key, and we talked a little bit earlier [about how] you have to individualize therapy. Dr Moore, how do the adverse event profiles of the 3 CKD4/6s compare and contrast with each other? …We talked about this a little bit more, but I think [it] would be great for you just to review it one more time with our audience.

Heather Moore, PharmD, CPP, BCOP: Yes. I think it’s really just taking an individual approach and looking at each individual agent. Like I mentioned, palbociclib,…is tolerated overall on a daily basis very well. And that’s what I tell patients when we start therapy: “On a daily basis, you’re going to tolerate this very well.” I think most of the [adverse] effects…going back to Dr DiMarco’s discussion on endocrine therapy…[aren’t] going to be much more than what we see from endocrine therapy. Aside from fatigue and also being mindful of myelosuppression, really the big things are knowing how to manage neutropenia, anemia, [and] thrombocytopenia, if you’re seeing those, but for the most part it is tolerated very well. I…think of it as [being] like a gentle giant. The next one is the ribociclib, and ribociclib on a daily basis is very similar [to] palbociclib, with the exception that you do have to be very mindful of QTc [corrected QT interval] prolongation, making sure that you’re doing the baseline monitoring. And I think…going back [to] some of that,… if we’re in large academic centers, it’s very easy––we have echo[cardiograph] and cardiac [departments] across the street…. They come over, do an ECG [electrocardiogram] in the room. But [if] we think about community practices, it’s much more difficult to get an ECG at baseline, mid-cycle, [or] end of cycle. Just thinking about the logistics of that sometimes can be tough. But then again, I think what’s really important is making sure that you’re identifying the right patient, especially because as we know, based off…the MONALEESA data…––MONALEESA-7, MONALEESA-2––and the overall survival data, and especially where it is placed right now on the NCCN [National Comprehensive Cancer Network] guidelines, we are going to use it more. So I think it’s important that we know how to monitor and then what we’re looking for in terms of QTcF [QTc using Fridericia correction]––450 baseline to start, 480 to continue. I think that’s something that also can be difficult to remember…making sure that you’re correcting for that, and if you have a patient with a history of AFib [atrial fibrillation], a patient [taking] metoprolol because of their AFib, [recognizing that] perhaps that’s not the best patient and knowing when to exclude them.

And then with abemaciclib, I think the biggest thing we have to be mindful of is diarrhea.... We’ve been using this drug for a while. We have experience in terms of management and now my goal is focused on how…we prevent [diarrhea] to begin with, and thinking more from the neratinib [adverse] effect of things. And I think we do have more data to support it now based on what was presented at ASCO [American Society of Clinical Oncology] with abemaciclib dose reductions [showing] that patients benefit regardless. So I think that’s comforting in some instances. But knowing what agents you can use, when it is going to start, [and] how patients can manage that at home, giving them those things up front [is important]. I send every patient a prescription for loperamide when they start; when they come in, they get a prescription for loperamide. We go over max[imum] doses, we go over when to call, when they can expect it, and then the what ifs of situations. Because I think patients feel comfort in knowing, if this happens, we have a plan. And then things that are less toxic that I didn’t hit on before but I think are important to know, [and] less common, are going to be…class effects.… Pneumonitis, while not very common, [I] have certainly seen…in clinic and [it can] certainly happen––it is a class effect––[and] also…VTE [venous thromboembolism]. We do see increased risk of clot with all…these agents, so [it’s] something to be mindful of. And then [there is] hepatotoxicity and that tends to be seen a little bit more with abemaciclib and ribociclib, which is why we also…see CMPs [comprehensive metabolic panels] in combination with their monitoring mid-cycle, end of cycle for those first 2 cycles. But I have seen very high levels of hepatic toxicity [in] patients with AST [aspartate aminotransferase and] ALT [alanine aminotransferase levels] in the 900s and thousands [range] sometimes, and [it’s important to know] how to manage that, what do you do, how do you approach that. And then, more importantly, if they were stable on therapy, how do you transition them? Because you want to keep them on a CDK4/6 inhibitor. And in those instances, we’ve transitioned to drugs like palbociclib that don’t have that [adverse] effect. So…it’s really important to…be familiar with the drugs and know how you’re going to dose change them, know how you’re going to address [adverse] effects, and then if something goes wrong, how you may switch between them.

Transcript is AI generated and edited for clarity and readability.

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