Dr Tolaney on Considerations for Adjuvant CDK4/6 Inhibitors in HR+/HER2-Negative Breast Cancer

"When we think about using a CDK, 4/6 inhibitor, there are a lot of factors that I am keeping in mind, but I think the biggest issue that I am thinking about is, what is this patient's risk of recurrence?"

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology, associate director of the Susan F. Smith Center for Women’s Cancers, and a senior physician at Dana-Farber Cancer Institute; and an associate professor of medicine at Harvard Medical School, discusses the key factors influencing the selection of adjuvant CDK4/6 inhibitors for patients with hormone receptor (HR)–positive, HER2-negative early-stage breast cancer.

The primary consideration for the use of one of these agents in theadjuvant setting is an individual patient's risk of recurrence, Tolaney explains, noting that CDK4/6 inhibitors are most beneficial in reducing recurrence risk in high-risk populations.

However, defining and standardizing risk remains a challenge, Tolaney explains, but clinical trial criteria provide general guidance. In the phase 3 monarchE trial (NCT03155997), which supported the FDA approval of abemaciclib (Verzenio) in combination with endocrine therapy for the adjuvant treatment of adult patients with HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence, high-risk disease was defined as 4 or more positive lymph nodes, or 1 to 3 positive nodes with additional risk factors, including tumor size larger than 5 cm or high histologic grade.. Conversely, the phase 3 NATALEE trial (NCT03701334) had broader eligibility criteria, and data from this study supported the FDA approval of adjuvant ribociclib (Kisqali) plus an aromatase inhibitor for the treatment of patients with HR-positive, HER2-negative, stage II and III early breast cancer at high risk of recurrence, including those with node-negative disease.

In clinical decision-making, Tolaney emphasizes evaluating whether patients meet eligibility criteria from these pivotal trials to help define those at high risk of recurrence. Generally, patients with lymph node involvement should be considered for adjuvant CDK4/6 inhibitor therapy, she says. In the absence of nodal involvement, other high-risk features, such as large tumor size, high genomic risk, or high-grade histology, are needed to consider a CDK4/6 inhibitor in the adjuvant setting, Tolaney concludes.