Kevin Kalinsky, MD, MS: We’ve known from metastatic disease that with CDK4/6 inhibitors there can be significant advantage of utilizing them in the metastatic setting.
And we’ve seen across the various studies in the metastatic setting progression-free survival benefit and for some of the agents an overall survival benefit. So there’s been a lot of interest about utilizing these agents in the early-stage setting.
And the data that we’ve seen with palbociclib [Ibrance] did not yield an improvement in invasive disease-free survival. But with monarchE we did see an improvement with invasive disease-free survival.
And how that study was designed, is that these were some higher risk patients and all those patients received endocrine therapy plus or minus 2 years of abemaciclib [Verzenio]. And these data have been updated, and recently published in the Annals of Oncology, demonstrating that those 2 years lead to an improvement in invasive disease-free survival.
The drug was approved based upon these data, meaning abemaciclib was approved in the early-stage setting in patients who are high risk, and by that I mean that they had a Ki67 that was 20% or greater and had 1 to 3 nodes involved. And had other high-risk features like grade 3 tumors or tumors that are greater than 5 centimeters. And the FDA [Food and Drug Administration] approved this particular agent in that setting and that’s what’s included in the label.
ASCO [American Society of Clinical Oncology] since has come out and been a little bit more open in terms of definition of high risk. But for this particular patient, she does meet these criteria of grade 2 tumor, 1 to 3 nodes involved, high Ki67. It would be totally appropriate to think about abemaciclib for this patient.
When doing an analysis looking at Ki67, what was seen, if you look in those different cohorts that had a lower Ki67 or a higher Ki67, the absolute benefit was different between the population.
So the population who had a higher Ki67 had a numeric benefit of invasive disease-free survival after about 3 years or so, of about 7%. And that was lower in the population who had a lower Ki67.
Though the hazard ratio is the same between those 2 populations, the FDA approved the drug in those patients who have a higher Ki67 because those patients have a higher risk.
And that lead towards that population having a higher numeric benefit in terms of the absolute benefit with the abemaciclib.
Transcript edited for clarity.
Case: A 67-Year-Old Woman with ER+/PR+ Breast Cancer
- A 67-year-old, postmenopausal woman presents with a newly diagnosed lump in her left breast
- She has 2 grown children, no family history of cancer, and underwent menopause at age 48
- PMH is significant for hypertension that is well controlled with medication
- Imaging demonstrated a 4.4-cm solid mass in the right upper quadrant with no suspicious adenopathy
- Core biopsy: positive for invasive ductal carcinoma, ER 100%/PR 40%; HER2 IHC 1+; Ki-67 30%; modified Bloom-Richardson grade 3
- Lumpectomy and sentinel lymph node biopsy performed
- Tumor size is 4.5 cm, and 2/5 LNs are positive for metastatic disease
- 21-gene recurrence assay score is 30
- T2N1M0, stage IIA
- ECOG PS is 0
- Patient underwent partial mastectomy with no residual disease
- She is started on adjuvant chemotherapy with cyclophosphamide and docetaxel
- She is given radiation therapy to intact breast
- Followed by aromatase inhibitor + 2 years of abemaciclib