Breast cancer experts discuss the role of biomarker testing in patients who receive a disease diagnosis.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Let’s talk a little bit about biomarkers. For this patient population, are there key biomarkers that we have to test for? I know Ki-67 to some extent has been looked at in clinical trials. Is that a driver in terms of prognosis for our patients or responses to CDK4/6s, Heather?
Heather McArthur, MD: Ki-67 is a well-established prognostic factor and is incorporated into some of the genomic assays like Oncotype, for example. So that’s one of the areas that’s interrogated. What’s been challenging with Ki-67 has been interobserver variability in terms of reporting and what the optimal threshold is for delineating high- versus low-risk. So there have been different studies that have used 20% versus 30%, for example, as cutoffs to identify patients at high risk, and different thresholds for low risk as well. So it’s been challenging, and it was a little bit challenging with the monarchE [NCT03155997] data when it was initially FDA-approved. The FDA elected to incorporate Ki-67 using the 20% cutoff that was used in monarchE for a selection of patients who could access adjuvant abemaciclib [Verzenio] initially. And a lot of sites weren’t actually testing for Ki-67, so that created some real-world clinical challenges for many sites. And again, Ki-67 has been as a test in of itself been fraught with some just technical challenges through the years. More recently, the FDA updated their approval so that now the approval for high-risk hormone receptor-positive HER2-negative early-stage breast cancer is agnostic of Ki-67. It was incredibly helpful that ASCO [American Society of Clinical Oncology annual meeting] and NCCN [National Comprehensive Cancer Network] actually in their guidelines after the FDA approval were also agnostic of Ki-67 from the onset. So it did empower us to get access to adjuvant abemaciclib for our high-risk patients, even if we didn’t have Ki-67 available at our locations. But the FDA did recently update their indication, so now it’s agnostic. I think it’s less potentially relevant in routine clinical practice at this time. And it does tend to highly correlate with grade, for example, which is done routinely as well.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Sarah, how do you identify these patients? Should all our early-stage breast cancer patients receive adjuvant CDK4/6, or is it the high-risk patient population? How does that work? And in terms of screening your patients, again we’re agnostic of Ki-67, but what type of screening modalities do you have in your clinic to identify those patients?
Sarah Sammons, MD: That’s a great question. Right now, today, all we have is adjuvant abemaciclib. The FDA approval of the Ki-67 requirement has been taken away since March 2023. And now it’s recommended for node-positive, high-risk patients. What does that mean? For me, I think about and I talk to my patients about the risks and benefits of abemaciclib in essentially cohort 1 of monarchE, which was those really high-risk patients with 4 or more positive nodes, with 1 to 3 nodes but other high-risk clinical pathological features, grade 3 disease, a T3 tumor. Their cohort 2, which was a very small portion of the clinical trial, included patients with 1 to 3 positive nodes with high Ki-67. We don’t test for Ki-67 at my institution, so that’s not a population that I’m currently offering it in. I’m in an academic institution and pretty close to the data. So when I’m thinking about a patient, I’m thinking about their clinicopathological features at their post-op appointment. And I’m writing in my note, this is what we’re doing. We’re going to talk at some point after radiation about adjuvant CDK4/6. And then a huge part of the health care system now is advanced practitioners. So my nurse practitioner knows the plan. She can bring it up. If I was ever out for any reason, the person that was covering my patients could bring it up. For now, there’s no way I screen other than just knowing the data. But I was very interested to hear that Jay’s institution has come up with screening and a very good way to identify these patients.
Jay Andersen, MD: I agree. I follow the same cohort 1 population. A question I want to ask and not forget to ask is about cohort 2, which you defined what that is, was not included in the approval because there was a signal of increased mortality events, 10 versus 5. And I’ve not heard any follow-up on that. I’m curious if anyone has. Initially, that group appeared to be benefiting when previous analyses that were read out. So I’m curious to come back to that. But to your question, we’re part of the US Oncology Network and in our EMR [electronic medical records] we have a pathway. And what we developed—I’m actually on the Pathways Task Force Committee—what we developed is shortly after the data came out, and it was approved when you enter all of your information, there’s a pop-up box that will appear. Once you’ve entered ER [estrogen receptor]-positive, HER2-negative, and staging information, etc., a pop-up box that says, “Is your patient high risk as defined by essentially cohort 1 definition?” And then if you aren’t aware of the data, you may say, “Oh, yes.” You click on it, and then it pops up on your menu of therapeutic options. So that is another way to keep physicians up to date and remind them of the opportunity.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: I’m under the same bucket of US Oncology, and that’s something that I think has been very impressive in how it’s integrated within the EMR, especially for those providers who are generalists that may not be well versed in some of the data and abreast in terms of these updates and these key updates that we’re discussing. To go back to your question and that cohort 2 population, has anybody heard anything further about it or…
Heather McArthur, MD: There was no update in the recently updated publication. I think it would be pure speculation at this point.
Transcript edited for clarity.