Massimo Cristofanilli, MD: Based on the monarchE [trial], since the moment of approval, I’ve presented patients with this option. A number of patients have started the treatment. Interestingly enough, there are a variability of adverse effects similar to what we’ve seen in the metastatic setting, which some patients do very well with. They adjust their diet, manage their diarrhea, and continue to do well after the first few weeks. Some patients have completed the 2 years without having further issues with bone marrow toxicity or diarrhea. Very few patients have significant toxicity from chemotherapy and radiation, and [it’s because] they simply couldn’t tolerate it. Not only [because of] diarrhea, but also they approached 2 years of more aggressive treatment, [which] at that point was too much to deal with. We need to pay attention to all these factors.

The majority of patients will be motivated and informed by the data. They’ll be motivated to the end because they understand the end goal is to improve or delay the recurrence and possibly eliminate [the breast cancer] and become certainly cured. At the same time, for a fraction of patients, the treatment has been somewhat difficult to handle with chemotherapy, so they’ll have difficulty later on. Taking 2 years of treatment probably isn’t for them.

Looking at the data, I also see that there weren’t many African American patients represented in monarchE. These patients are sometimes not as willing to take more treatments. How do we explain the [lack of] diversity in the study [but show that the treatment] benefits them? They have more questions. That’s an area that we need to make some effort in, suggesting that these data apply to their population. This is a major advancement in treatment. At some point, we’re going to have support of the data showing that possibly overall survival is improved. It’s too early to say. But the difference is a tremendous opportunity. We need to make sure the patient understands the advantage.

Sara Tolaney, MD, MPH: That’s an excellent point. It’s interesting, we did an analysis from monarchE in which we looked at predictors of people who were able to stay on therapy and tolerate therapy compared with those who discontinued treatment early. One factor that came up was that having higher-risk disease led to fewer discontinuations. To your point, when people understand that they have high-risk disease, they’re more willing to think about ways to deal with the medication. We’ve learned a lot about abemaciclib management, and we’ve also learned what a tremendous advantage it has in terms of risk reduction. Because if you can tell a high-risk patient that it’s going to reduce their risk by a third, that’s a very large advantage. Unfortunately, that recurrent disease is metastatic disease, which we’re unable to cure. We want to prevent those events.

One thing I learned from monarchE was that it’s important to inform patients of toxicities up front and to make sure you communicate carefully with them. One of the problems in monarchE is that a lot of patients discontinued therapy without dose modification, even though dose modification works. I’m in good communication with that patient, particularly in the first 2 weeks, because their median time to onset of diarrhea is day 8. If you can catch that patient when they seem to experience adverse effects, hold their drug, and dose modify if needed, then they do well. In fact, when you look at the monarchE toxicity data, you’ll see that the majority of diarrhea occurs in the first month or so. After 3 months, people have no diarrhea or grade 1 diarrhea. You’re not seeing problems with persistent high-grade diarrhea. There’s also tachyphylaxis over time, but patients learn how to manage it with dose modification or with the use of, for example, loperamide, which works quite well. This issue about informing patients and dose modification is critical.

The other thing that’s important to warn your patients about is the rare risk of ILD [interstitial lung disease]. It’s in just a couple of percentage points of patients, but it isn’t a toxicity we’re used to thinking about with CDK4/6 inhibitors. We need to be aware of it.

The other thing with abemaciclib is a risk of VTE [venous thromboembolism]. It wasn’t so common, but it was more common with the tamoxifen combination relative to AI. There’s a 4% incidence of VTE with tamoxifen compared with under 2% with AIs [aromatase inhibitors]. I tend to avoid tamoxifen. Most of the time, these are high-risk patients. Even if they’re premenopausal, I would have given them ovarian suppression and an AI anyway, but that’s 1 thing to keep in mind.

Massimo Cristofanilli, MD: And you raised the point of [patients with] high risk adhering to the treatment. Essentially the majority, if not all patients with inflammatory whom I treat get to that situation where they can be treated with abemaciclib. They haven’t dropped the drug because they understand the high risk of this condition, that when you have residual disease in inflammatory cases, even if it's ER [estrogen receptor] positive, you have a very high risk of recurrence. And whatever we can do to reduce the risk of recurrence, we'll take it. Those populations are very motivated. Of course, as you mentioned, we work with them and try to reduce the adverse effects, especially the diarrhea. So it's really important. If it's a patient that has a Ki-67 around 25% and 1 lymph node, they understand that there is an advantage in a small subset, but maybe they're less willing to take all 2 years of treatment.

Sara Tolaney, MD, MPH: It's the first time we've had an approval for an agent in the adjuvant ER positive setting in decades, outside of endocrine therapy. It’s really nice to have another tool in our armamentarium to really reduce risk, which is great. But it’s important to keep those management techniques in mind.

Transcript edited for clarity.