Managing Abemaciclib-Associated Toxicities in HR+/HER2- Early Breast Cancer


VK Gadi, MD, PhD, shares his strategies for managing adverse events related to abemaciclib in the treatment of HR+/HER2- breast cancer.


Komal Jhaveri, MD, FACP: VK, we were talking about the toxicity with ribociclib, and we were talking about LFT [liver function test] elevations and QTc prolongations and requirement for EKGs. What about for our approved agent abemaciclib based on the monarchE trial [NCT03155997], I think we all know that diarrhea is the most important [adverse] effect. How do you think about that diarrhea? How do you manage your patients? What do you think is important? Maybe in that context also review the data that Dr Erika Hamilton presented by age subgroup analysis from the monarchE [study].

VK Gadi, MD, PhD: I’ll start with the last part of that question. If people read through this abstract and watch the presentation, what you realize is not surprisingly with older patients, these toxicities are more often the case. That might be for a multitude of reasons, including things like polypharmacy and other stuff that we haven’t explored. But we have to know that as patients get older, these toxicities are easier to come by. Plus you can imagine younger folks…may be able to minimize grade 2 toxicity, whereas it’s harder in an older person to minimize that. And so you can see maybe even a higher discontinuation rate in an older patient population because even at a lower toxicity, it’s just harder for them to do. That’s kind of what we learned from that.

Just stepping back then and thinking about how to counsel patients, I think this is the toxicity that we have to focus on. In our practice, we work on provider education so that our other providers who are working with us can keep the patient [looking at treatment] in a positive light and spin. We definitely want to be prophylactically providing agents to help with these problems as they arise. There might be other strategies that we can explore through clinical studies, etc, and learn what might be some other ways to control this. But I will say just now that we have ribociclib available potentially in a few years based on the data from NATALEE [NCT03701334]. I’ve already done this thought experiment about what it’s going to be like to have this discussion with a patient. You have, on the one hand, 2 years of treatment vs 3, but on the other hand, you have a drug that might have more neutropenia associated with it. In a patient population that’s predominantly African American, we worry about things like benign ethnic neutropenia and triggering neutropenia in this context, which may not be therapeutically important, but certainly would lead to even more dose reductions, etc. So I’m starting to do this exercise and it’ll be interesting once the agents are both available, which is a great luxury to have 2 agents. But there are these subtleties that I think we’re all going to have to [talk about] with our patients. It’s going to be a discussion.

Komal Jhaveri, MD, FACP: I think you absolutely said it right. I think it’s going to be an individualized approach for a given patient depending on what baseline comorbidities they have, what kind of profession they’re in, what their age is, what we expect with them, and what their experience with a given drug is and what their preferences are. Because I think, ultimately, it’s going to be a shared decision-making process that we will have [with] our patients. But it is the embarrassment of riches to have more drugs to offer our patients once we have them.

Timothy Pluard, MD: Just following up on what VK said about educating the patients about what to expect, I think one of the takeaways from Erica’s presentation was that patients discontinued without dose reduction. So, it was kind of an all-or-nothing for them. They’re either in or they’re out without recognizing perhaps that lowering the dose would mitigate some of the toxicity and still allow them to stay on trial or therapy. The other thing is we potentially look at ribociclib in the adjuvant setting. The context of the oncology-patient relationship in the adjuvant setting is a little bit different than it is in the metastatic setting. So even though we assess their QTc interval at the beginning, they’re seeing a lot of other providers, and they may get other drugs that prolong the QTc interval. So we have to educate the patients on that. Even antibiotics can do that. We [must] be wary of that as well.

Komal Jhaveri, MD, FACP: I think [those are] excellent points that you’ve made.

Transcript edited for clarity.

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