Dr Shen on Adjuvant CDK4/6 Inhibitors in HR+/HER2– Breast Cancer

Sherry Shen, MD, assistant attending physician, breast oncologist, Memorial Sloan Kettering Cancer Center, discusses findings from the phase 3 monarchE (NCT03155997) and NATALEE (NCT03701334) trials evaluating adjuvant CDK4/6 inhibitors in patients with early-stage, hormone receptor (HR)–positive, HER2-negative breast cancer.

The monarchE study evaluated abemaciclib (Verzenio) in combination with endocrine therapy, and findings from the trial supported the October 2021 FDA approval of combination for the adjuvant treatment of adult patients with HR-positive, HER2-negative, node-positive, early-stage breast cancer at high risk of recurrence and a Ki-67 score of 20% or higher, as determined by an FDA-approved test. An expansion of this indication in March 2023 removed the Ki-67 requirement.

NATALEE explored the addition of ribociclib (Kisqali) to a nonsteroidal aromatase inhibitor (NSAI) for the treatment of patients with HR-positive, HER2-negative early-stage breast cancer. Findings published in the New England Journal of Medicine showed that patients who received the combination (n = 2549) achieved a 3-year invasive disease-free survival rate of 90.4% compared with 87.1% among those who received an NSAI alone (n = 2552; HR, 0.75; 95% CI, 0.62-0.91; 2-sided P = .003).

Currently, abemaciclib is the only CDK 4/6 inhibitor approved by the FDA for adjuvant use in patients with HR-positive, HER2-negative early-stage breast cancer, Shen explains. This status makes abemaciclib the primary treatment choice eligible patients in this population, noting that she ensures patients fit the inclusion criteria for monarchE when determining whether to use this treatment approach.

Although adjuvant ribociclib has not received FDA approval, a green light for adjuvant use could expand the therapeutic options available, offering another adjuvant treatment with a distinct toxicity profile, Shen continues. Furthermore, she explains the broader eligibility criteria in the NATALEE study might allow for the inclusion of a wider range of patients for treatment with adjuvant ribociclib compared with abemaciclib.

This distinction in eligibility and the differing toxicity profiles between the two drugs highlight an evolving landscape in the treatment of HR-positive breast cancer, where personalized treatment decisions could be influenced by both the clinical characteristics of the disease and the safety profiles of the available medications, Shen concludes.