Targeted treatment with ribociclib plus hormone therapy provided significant invasive disease-free survival (iDFS) benefits in patients with early-stage hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) 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 today at the 2023 San Antonio Breast Cancer Symposium (SABCS).
Patients who received the combination therapy experienced significantly extended iDFS - the period before the first occurrence of invasive disease - compared to those who underwent hormone therapy alone, which corresponds to a 25% reduction in the risk of recurrence. The iDFS rates at three years were 90.7% with the combination and 87.6% with only hormone therapy.
"The current treatments we have for HR+/HER2- 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, M.D., professor of Breast Medical Oncology. "This study shows the continued disease-free survival improvement for patients receiving ribociclib with hormone therapy and showed a benefit across clinically relevant subgroups."According to the National Cancer Institute, HR+/HER2- breast cancer is the most common subtype, accounting for nearly 70% of all breast cancer cases in the United States. Approximately one-third of individuals diagnosed with stage II HR+/HER2- 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. The Food and Drug Administration has granted approval for ribociclib's use in treating advanced HR+/HER2- breast cancer. While previous research led by Hortobagyi demonstrated the survival advantages of ribociclib in treating metastatic breast cancer, this trial provided evidence that it could improve outcomes for patients with early-stage breast cancer that hasn't spread to the lymph nodes.
The NATALEE trial enrolled 5,101 men and pre-/post-menopausal women from 20 different countries with stage IIA, IIB, or III HR+/HER2- breast cancer at risk for recurrence. Participants were randomized to receive either adjuvant ribociclib for three years with hormonal therapy for at least five years or hormonal therapy alone for at least five years. The primary endpoint was iDFS, and the secondary efficacy endpoints were recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS).
Researchers observed consistent benefits across patient subgroups, including those with node-negative, stage II and stage III disease. Analyses of secondary endpoints of DDFS and RFS supported ribociclib with hormone therapy compared to ribociclib alone. The overall survival data remains incomplete as of now, with 84 patients 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 non-steroidal aromatase inhibitors.
"I am encouraged by the results of this treatment combination in early-stage breast cancer patients," 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.
The study was sponsored by Novartis Pharmaceuticals, which markets ribociclib (Kisqali). Hortobagyi is a paid consultant for Novartis, and MD Anderson received funds from Novartis to conduct this study. A complete list of collaborating authors and disclosures can be found in the abstract.
