Updated Results of MonarchE in HR+ Breast Cancer

Sara Hurvitz, MD: Let’s move now into higher-risk patients, relating to advanced breast cancer and CDK4/6 inhibitors. The profound benefit in the metastatic setting, of course, has made everyone eager to see their use for the highest-risk patients in the adjuvant setting. Sara, can you take us through some of those data that have just come out? Let’s first address the monarchE trial, which was updated at the San Antonio Breast Cancer Symposium, initially presented at ESMO [European Society for Medical Oncology annual meeting], and recently updated. Can you give us some indications of the design of the study, the type of patients who are enrolled, and what the top-level results showed?

Sara M. Tolaney, MD, MPH: Just as you alluded to, I think we’ve all been eagerly awaiting these data because we saw such a large benefit in the metastatic setting from these agents. We’ve been really hoping that using CDK4/6 inhibition in the adjuvant setting would yield similar benefits and help us prevent recurrence. MonarchE looked at adding abemaciclib to endocrine therapy in the adjuvant setting, but was specifically addressing what they considered high-risk ER-positive patients. The trial was specifically designed to look at patients who met these high-risk criteria, which were defined to be a patient who had 4 or more positive lymph nodes, or could have 1 to 3 positive nodes but had to meet an additional criterion. So you either had to have a tumor over 5 cm, be high grade, or have a high Ki-67.

Those high-risk patients then got randomized to receive endocrine therapy with or without abemaciclib. As you would imagine, the vast majority, about 95% of patients in this study, had received chemotherapy, again knowing that they had high-risk disease. But then it was really asking if we can prevent recurrence by adding abemaciclib to the endocrine treatment? As you noted, the initial data from the interim analysis had been presented at ESMO, which only had 15 months of follow-up at that time, but did suggest an absolute difference of about 3.5% between the 2 arms, about a 25% reduction in risk of recurrence.

But I think we were all a little bit worried because at that presentation, three-fourths of the patients were still on their 2 years of abemaciclib. They hadn’t even completed their adjuvant treatment. The trial had a primary outcome analysis that was event driven and came out at 19 months of follow-up. And those data were presented just recently at San Antonio, so not that much longer follow-up at this point. About 56% of patients were still on their 2 years of adjuvant abemaciclib, so again, about half of the people haven’t completed their 2 years of treatment.

But at this point we still see benefit, now almost 30% relative risk reduction in terms of recurrence, with about a 3% absolute difference, favoring abemaciclib, suggesting that abemaciclib can help us prevent recurrence in these high-risk patients. I think these data have been very exciting. We’ll talk about data from other studies and how that may put some of these data into light. Because I think one question is, are these mature enough data for us to really know we’re preventing recurrence? Is it possible that we are controlling micrometastatic disease, and that if we were to stop abemaciclib, would the curves come back together again?

I think that still is a very valid question that one has to consider. Again, patients still are on abemaciclib at this point, and we do need longer follow-up. That being said, these are very high-risk patients where events typically occur early. At this point, our only real treatment for them is endocrine treatment. I’ve been very excited about these data but do want to see the longer follow-up.

There obviously are toxicities. Any time we add treatment, we’re going to see some adverse effects, but I think, generally speaking, it was pretty well tolerated. The rate of discontinuation due to adverse events was a little under 20%. Still we’re going to see that number go up because patients are still on treatment, but most of the discontinuation happened early, predominantly within the first 6 months of therapy. Rates of grade 3 diarrhea from abemaciclib are very low, under 10%. It seems like it’s doable and tolerable, but again, I think we need longer-term follow-up to know for certain if we are preventing recurrence.

Transcript edited for clarity.