Dr. Erika Hamilton on Updated Results From monarchE Presented at ESMO 2025
Key Points
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Long-term data show CDK4/6 inhibitors improve outcomes for hormone receptor (HR)-positive, HER2-negative (HR+/HER2-), high-risk, early breast cancer.
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Abemaciclib plus endocrine therapy (ET) showed an overall survival (OS) benefit compared with ET alone in the phase 3 monarchE trial.
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In the phase 3 NATALEE trial, ribociclib plus nonsteroidal aromatase inhibitor (NSAI) increased disease-free survival (DFS) versus NSAI alone.
CDK4/6 Inhibitor Treatment in High-Risk Early Breast Cancer
Erika Hamilton, MD, and Sarah Premji, MD, both of the Sarah Cannon Research Institute, met to discuss two notable conference updates on CDK4/6 inhibitor therapies for breast cancer from the European Society of Medical Oncology (ESMO) Congress 2025. The monarchE trial evaluated adjuvant abemaciclib plus ET in hormone receptor HR+/HER2-, node-positive, high-risk, early breast cancer. The NATALEE trial evaluated adjuvant ribociclib plus NSAI in a similar population to monarchE, though NATALEE also enrolled some node-negative patients.
Updated Abemaciclib Outcomes From monarchE
The ESMO Congress 2025 presentation on the monarchE trial provided updated outcomes after a median follow-up of 76.2 months. The abemaciclib plus ET group had a significantly lower risk of death compared with the ET group (hazard ratio [HR], 0.842; 95% CI, 0.722-0.981; P = .027). Abemaciclib plus ET also showed sustained improvements in invasive DFS (IDFS; HR, 0.734; 95% CI, 0.657-0.820) and distant relapse-free survival (DRFS; HR, 0.746; 95% CI, 0.662-0.840).
The 7-year OS rate with abemaciclib plus ET was 86.8% versus 85.0% with ET alone. Though the benefit may seem small, “when abemaciclib and ET are already FDA approved in the first-line setting and the average survival for HR-positive metastatic breast cancer is in excess of 5 years, to already see this survival benefit with only 6 years of follow-up is really impressive,” Dr. Hamilton said.
NATALEE Trial Results for Ribociclib in Breast Cancer
The NATALEE data update covered a median follow-up of 55.4 months, and reported adjuvant ribociclib plus NSAI continued to show a persistent IDFS benefit compared with NSAI (HR, 0.716; 95% CI, 0.618-0.829; P < .0001) across subgroups, including node-negative disease (HR, 0.606; 95% CI, 0.3722-0.986). The 3-, 4-, and 5-year absolute rates of IDFS for ribociclib plus NSAI versus NSAI alone were 90.8% versus 88.0%, 88.3% versus 83.9%, and 85.5% versus 81.0%, respectively. Ribociclib plus NSAI showed further gains compared with NSAI alone in distant DFS (HR, 0.709; 95% CI, 0.608-0.827) and DRFS (HR, 0.699; 95% CI, 0.594-0.824) outcomes.
“Even though some of the patients were a bit lower-risk in [NATALEE] than monarchE, they’re deriving benefit as well, so I think it’s really important to discuss [ribociclib plus NSAI] with our patients,” Dr. Hamilton said.
Selecting Patients for Abemaciclib or Ribociclib
The side effect profiles and treatment lengths may influence the choice between abemaciclib and ribociclib in patients eligible for both. In this setting, ribociclib is administered for 3 years, while abemaciclib is given for 2 years. Abemaciclib is associated with diarrhea and gastrointestinal (GI) effects. Comparatively, ribociclib is associated with less GI effects but greater neutropenia, but ribociclib requires monitoring for liver function and QTc interval effects in the initial treatment period. Selecting abemaciclib or ribociclib in a patient eligible for both should be an informed, shared decision with the patient based on these drug characteristics.
The Future of HR+/HER2-, High-Risk, Early Breast Cancer Trials
While there are some signals that patients who relapse after receiving CDK4/6 inhibitor therapy have more aggressive disease, the data showing potential curative benefit of these treatments support their continued use in early lines of therapy. In that sense, the focus for research may be on novel ET agents or targeted therapies, said Dr. Hamilton.