Combining Ribociclib With Hormone Therapy Improves Patient Outcomes in Early-Stage Breast Cancer: NATALEE

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Targeted treatment with ribociclib plus hormone therapy provided significant invasive disease–free survival benefits in patients with early-stage hormone receptor–positive, HER2-negative breast cancer at risk of disease recurrence. Results from the phase III NATALEE trial, led by researchers at The University of Texas MD Anderson Cancer Center, were presented at the 2023 San Antonio Breast Cancer Symposium (Abstract GS3-03).

Patients who received the combination regimen experienced significantly extended invasive disease–free survival compared to those who received hormone therapy alone, which corresponds to a 25% reduction in the risk of recurrence. The invasive disease–free survival rates at 3 years were 90.7% with the combination and 87.6% with only hormone therapy.

Gabriel Hortobagyi, MD

Gabriel Hortobagyi, MD

"The current treatments we have for hormone receptor–positive, HER2-negative early-stage breast cancer only help a small group of patients, which leaves many people with limited options to lower the chances of their cancer coming back,” said Gabriel Hortobagyi, MD, Professor of Breast Medical Oncology at MD Anderson. “[NATALEE] shows the continued disease-free survival improvement for patients receiving ribociclib with hormone therapy and showed a benefit across clinically relevant subgroups.”

Study Background

According to the National Cancer Institute, hormone receptor–positive, HER2-negative breast cancer is the most common subtype of the malignancy, accounting for nearly 70% of all breast cancer cases in the United States. Approximately one-third of individuals diagnosed with stage II hormone receptor–positive, HER2-negative breast cancer face a risk of recurrence, despite receiving standard-of-care treatment. Among those with stage III disease, more than half experience a recurrence.

Ribociclib belongs to a category of targeted therapies known as small-molecule inhibitors. It specifically targets the CDK4 and CDK6 proteins, which play a crucial role in regulating cell growth and promoting the growth of breast cancer cells. In 2018, the U.S. Food and Drug Administration granted approval for ribociclib's use in treating advanced hormone receptor–positive, HER2-negative breast cancer. While previous research led by Dr. Hortobagyi demonstrated the survival advantages of ribociclib in treating metastatic breast cancer, the NATALEE trial provided evidence that it could improve outcomes for patients with early-stage breast cancer that hasn’t spread to the lymph nodes.

NATALEE Methodology

The NATALEE trial ( identifier NCT03701334) enrolled 5,101 men and pre- and postmenopausal women from 20 different countries with stage IIA, IIB, or III hormone receptor–positive, HER2-negative breast cancer at risk for recurrence. Participants were randomly assigned to receive either adjuvant ribociclib for 3 years with hormonal therapy for at least 5 years or hormonal therapy alone for at least 5 years. The primary endpoint was invasive disease–free survival, and the secondary efficacy endpoints were recurrence-free survival, distant disease–free survival, and overall survival.


Researchers observed consistent benefits across patient subgroups, including those with node-negative, stage II, and stage III disease. Analyses of secondary endpoints of distant disease–free survival and recurrence-free survival supported ribociclib with hormone therapy compared to ribociclib alone. The overall survival data remains incomplete as of now, with 84 events in the ribociclib plus hormone therapy group and a total of 88 events in the hormone therapy alone group.

No new safety signals were observed since the prior interim analysis, and side effects were consistent with the known safety profile of ribociclib and nonsteroidal aromatase inhibitors.

“I am encouraged by the results of this treatment combination in [patients with] early-stage breast cancer,” Dr. Hortobagyi said. “We will continue to follow the patients long-term, but these results could impact how we treat this disease in the future.”

Researchers will continue to evaluate how adding ribociclib to hormonal therapy impacts quality of life and will follow patients to observe long-term outcomes.

Disclosure: The study was sponsored by Novartis Pharmaceuticals, which markets ribociclib. Dr. Hortobagyi is a paid consultant for Novartis, and MD Anderson received funds from Novartis to conduct this study.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.