Using the monarchE trial as a benchmark, experts in oncology discuss the use of abemaciclib with adjuvant endocrine therapy in patients with high-risk, early stage HR+ breast cancer.
Sara Tolaney, MD, MPH: Let’s say this patient finished her chemotherapy and had a high recurrence score. She got some chemotherapy, and you’re making your decision about adjuvant endocrine therapy. She’s postmenopausal. She did have 1 positive node and a tumor that was 2.5 cm and grade 2. What do you think about the use of abemaciclib given the monarchE eligibility? Would you use it in this situation? She didn’t technically meet the cohort 1 eligibility because her tumor wasn’t over 5 cm. She didn’t have a high-grade tumor. But she meets eligibility for cohort 2 in the monarchE study, which was for individuals who had 1 to 3 positive nodes but had a tumor that wasn’t 5 cm or high grade. She fits in that bucket because she had that high Ki-67.
We have a little more limited data in that group of patients because we saw the updated data from monarchE at San Antonio [Breast Cancer Symposium]. They have some follow-up data from the cohort 2 patients, but the study was only 500 patients. It’s got very wide confidence intervals. Although the trend shows significant benefit, it’s hard to know what that true benefit is. Overall, monarchE has a one-third risk reduction in recurrence. But most of that is being driven by cohort 1. How would you think about this patient?
Massimo Cristofanilli, MD: This is a case in which you need to work with patients and explain what their options are. Assuming that she has a high recurrence score after the Oncotype DX testing, we know that a fraction of patients have a recurrence later in spite of chemotherapy. What else can we do for a reduction of risk in a patient without complete coverage and risk reduction by standard endocrine therapy? In monarchE, we had a very small fraction of patients, and she may seem to be qualified. It was 20%, and now it’s 46%. Obviously, she’s in the high end. Clearly, she’s one of those patients who could benefit. But we don’t have the data for a large cohort.
It would be nice if we could gather real-world data because abemaciclib is used in a much larger and open way compared with the small cohort of the study. In fact, the FDA opened up [the opportunity] for this type of patient to have this drug, especially when the risk is present and recognized. I’ll expose her to these data. I’ll discuss risk reduction. I’ll discuss the toxicity. We know that 2 years of treatment with abemaciclib is a commitment. It comes with some adverse effects that some patients are willing to accept. As we know, patients sometimes can take a 1% or 2% risk reduction—whatever it takes. Others aren’t willing to compromise quality of life. As I said, [because we don’t have] a large cohort of patients from the phase 3 study, it would [require] an open conversation with the patient. In the future, we’ll have enough data to decide which patients are candidates for that.
Also, in the monarchE, we didn’t have the recurrence score data. How do we reconcile the recurrence score, the Ki-67, and the prospective information about the outcome of these patients? Our field is evolving, and all the molecular tests, clinical information, and pathology need to come together. Although we can’t validate everything, we can integrate as much as possible.
Sara Tolaney, MD, MPH: That’s a good point. Things are going to evolve. I’m curious to see if the FDA will update the label for monarchE given the data we saw at San Antonio. One concern with the initial monarchE presentation was that there wasn’t a trend toward overall survival [OS] at that initial time point upon regulatory approval. While there’s still no OS benefit—truthfully, I wouldn’t expect there to be at 4 years of follow-up in an adjuvant ER [estrogen receptor]–positive setting—you see half the number of patients with metastatic breast cancer in the abemaciclib compared with the control arm. The point estimate is no longer 1 for OS. I wonder if that could influence them. The benefit is irrespective of Ki-67, and the relative benefit was the same in the high and low Ki-67 patients. I hope that changes, because we see benefit irrespective of Ki-67. Hopefully that will change with time. But it’s nice to see longer follow-up data.
Transcript edited for clarity.