Stephanie Graff, MD, and Rachel Layman, MD, discuss the design and results of the monarchE trial, which evaluated abemaciclib plus endocrine therapy for HR+, HER2 negative, node positive, high-risk early breast cancer.
Stephanie Graff, MD, FACP: The next question is what do we do for CDK [cyclin-dependent kinases] 4/6 inhibitors in the adjuvant high-risk population? What’s your approach here, Dr Layman?
Rachel Layman, MD: I’m currently using adjuvant abemaciclib for 2 years, similar to what was done in the monarchE clinical trial [NCT03155997]. The monarchE was an open-label randomized phase 3 trial, and it evaluated adjuvant abemaciclib in patients with hormone receptor–positive [HR+], HER-negative [HER–], and lymph node–positive breast cancer that had a high risk of recurrence. This was a very large study. Over 5000 patients were randomized, and they received standard-of-care endocrine therapy with or without abemaciclib at the standard dose of 150 mg twice per day, given for 2 years. In this study, the endocrine therapy consisted of tamoxifen or an aromatase inhibitor for 5 to 10 years; the treating physician was permitted to choose what they thought would be the best endocrine therapy for their patient. For premenopausal women, ovarian suppression was also permitted.
In this study, high risk was defined as 4 or more lymph nodes involved with cancer. Or if patients had fewer lymph nodes involved, 1 to 3, they had to have another high-risk feature. The tumor had to be over 5 cm or grade 3. This was really cohort 1, and this was the cohort that comprises the majority of the population. About a year after the study was opened, a second cohort was initiated. In this cohort patients only needed to have 1 to 3 positive lymph nodes, and they did not need that other high-risk feature of a large tumor or a high-grade tumor. However, in these patients, Ki-67 [score] had to be at least 20%. So our patient would definitely meet the criteria for adjuvant abemaciclib.
We saw that the adjuvant abemaciclib is quite effective and can really improve the outcomes for these patients. Recently, there was a 4-year update of the clinical trial. And in that report, the primary end point, which was invasive disease-free survival [DFS], was significantly improved, with a hazard ratio of 0.66. And the absolute improvement in invasive DFS was 6.4%. What I thought was really interesting and very important is that, as the data was reviewed,…the absolute benefits increased over time, and it persisted and even improved after the study therapy was complete. I thought that was really encouraging and demonstrated that this will likely make a very big impact on these patients. Other outcomes such as distant relapse-free survival were also similarly improved; overall survival is a little bit immature at this time so we can’t comment on that quite yet.
The other thing that was recently reported in the most recent update was more information about Ki-67 and in cohort 1, where patients could be high risk regardless of their Ki-67 status, the invasive DFS was improved in both populations of high and low Ki-67 breast cancers. So based on all of this data, I would certainly offer this patient the 2 years of adjuvant of abemaciclib.
Stephanie Graff, MD, FACP: So let me say it all back to you. You are not using Ki-67 as a key deciding point on whether or not your patient should get abemaciclib adjuvantly. If you have a patient with positive lymph nodes or a large tumor, even if their Ki-67 is 4, you would still offer them adjuvant abemaciclib.
Rachel Layman, MD: I would, based on the data, and I think how strongly you’re going to recommend this to the patient will be based on all of the prognostic features of the cancer. The absolute benefit is probably not as large as it is with patients with high Ki-67, but that’s also looking at the first 4 years where Ki-67 that is high may be a cancer that is going to recur earlier rather than later. So we don’t know what the data will look like as it continues to be followed, and the FDA [US Food and Drug Administration] recently removed the requirement for Ki-67 in March. So, prior to this, Ki-67 was part of the FDA approval, but now that that criteria has been removed, I think we can offer [abemaciclib] to our patients.
Transcript edited for clarity.