Dr Callahan on the Use of CDK4/6 Inhibitors Plus Endocrine Therapy in Breast Cancer

“The 4-year results [of the NATALEE trial] just provide extra confidence in using the approach of adding adjuvant CDK4/6 inhibitors to endocrine therapy.”

Rena D. Callahan, MD, a breast medical oncologist at UCLA Health and an associate clinical professor of medicine at the David Geffen School of Medicine at UCLA, emphasized the clinical confidence provided by the 4-year results of the phase 3 NATALEE trial (NCT03701334) regarding the adjuvant use of the CDK4/6 inhibitor ribociclib (Kiaqali) in combination with endocrine therapy in patients with hormone receptor (HR)–positive, HER2-negative early breast cancer.

Callahan highlighted that a consistent story has emerged from the analysis of major CDK4/6 clinical trials in breast cancer, specifically citing the phase 3 monarchE trial (NCT03155997) involving abemaciclib (Verzenio) and the NATALEE trial involving ribociclib. Callahan observed that when a CDK4/6 inhibitor is added to the treatment regimen for a patient with early-stage HR-positive breast cancer characterized by high-risk features, a substantial and growing difference in relapse rates is observed over time.

Callahan pointed out that the more time that has elapsed from the initiation of therapy, the greater the statistical differences become between outcomes in patients receiving endocrine therapy alone vs those receiving the combination of endocrine therapy and a CDK4/6 inhibitor. This trajectory, according to Callahan, underscores the necessity of long-term data to validate whether the intervention’s effects are merely protective during the active duration of the therapy, or if they offer lasting, durable benefits. Callahan noted that in the NATALEE trial, the prescribed duration of ribociclib therapy was 3 years; therefore, establishing efficacy beyond this time point was critical to prove that the intervention provides a sustained benefit that persists after the patient has finished treatment. Furthermore, Callahan addressed the broad clinical implications of these findings, noting that the NATALEE trial’s inclusion of patients with node-negative breast cancer significantly expands the potential treatment population that can benefit from this regimen.