NATALEE and Other Updates for HR+ Early Breast Cancer at SABCS 2025
Key Points
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The 5-year analysis from the NATALEE trial showed that adjuvant ribociclib provided a survival benefit even in node-negative high-risk breast cancer.
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Ribociclib has slightly broader eligibility criteria than abemaciclib, but in patients eligible for both, the choice between them is largely driven by the distinct side effect profiles.
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Oral selective estrogen receptor degraders (SERDs) show promise in recent data, though more research is needed to integrate SERDs with CDK4/6 inhibitors.
Adjuvant Ribociclib and Oral SERDs in Early Breast Cancer
Two breast medical oncologists, Komal Jhaveri, MD, FACP, of Memorial Sloan Kettering Cancer Center, and Matthew Kurian, MD, of St. Elizabeth Healthcare, gathered at the 2025 San Antonio Breast Cancer Symposium (SABCS 2025) to discuss updates from the NATALEE and lidERA trials.
Ribociclib has already been adopted for adjuvant treatment of HR-positive, HER2-negative early breast cancer based on previous analyses from the NATALEE trial. At SABCS 2025, NATALEE investigators presented the 5-year analysis from the trial, including distant disease-free survival (DDFS) across key subgroups.
What was most impressive in this presentation was the DDFS benefit in patients with node-negative disease (hazard ratio, 0.539; 95% CI, 0.318-0.913). While the NATALEE data on ribociclib are not as mature as the monarchE trial’s data on abemaciclib, the NATALEE findings are following a similar course, and both trials’ findings have reassured oncologists that adjuvant therapy with CDK4/6 inhibitors is effective for HR-positive, HER2-negative early breast cancer, said Dr. Jhaveri.
Some patients are only eligible for ribociclib because of the NATALEE trial’s broader inclusion criteria. For patients eligible for both ribociclib and abemaciclib, the choice of agent should be a shared decision with the patient based on tolerability and quality of life. Ribociclib is associated with less diarrhea than abemaciclib, though monitoring for neutropenia, liver function tests, and QTc interval prolongation is required.
Drs. Kurian and Jhaveri also considered the ongoing research into oral SERDs in HR-positive early breast cancer, including giredestrant in the lidERA trial. The SERD class is an exciting option that could impact the adjuvant endocrine therapy landscape, which has been largely unchanged for multiple decades. Ongoing studies will hopefully be able to determine how CDK4/6 inhibitors and oral SERDs fit together in the treatment paradigm for HR-positive breast cancer, Dr. Jhaveri said.