Introduction
The majority of breast cancer cases are nonmetastatic, potentially curable with locoregional treatments like surgery or radiation therapy. However, recurrences remain a significant issue, with endocrine therapy (ET) being the backbone of adjuvant treatment for HR+/HER2− breast cancer. Despite 5 years of standard ET, a considerable risk of recurrence persists, highlighting the need for effective adjuvant treatments.
CDK4/6 Inhibitors in Breast Cancer
Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, including ribociclib, have shown promise in advanced breast cancer (ABC), with ribociclib demonstrating significant overall survival (OS) benefits. This success has prompted investigations into their use in EBC, with varying results from Phase III trials. Notably, the monarchE trial showed that abemaciclib plus ET significantly improved invasive disease-free survival (iDFS) in high-risk HR+/HER2− EBC patients.
The NATALEE Trial
The NATALEE trial is evaluating ribociclib plus ET in a broad population of HR+/HER2− EBC patients, including those with node-negative disease and additional high-risk features. The trial's design, with a 3-year duration of ribociclib treatment, aims to maximize time-on-target exposure to ribociclib, potentially reducing recurrences by inducing senescence in circulating tumor cells.
Safety and Quality of Life
Ribociclib's safety profile is well-documented, with manageable adverse events (AEs) and maintained or improved quality of life (QOL) in ABC patients. The reduced starting dose of ribociclib in the NATALEE trial is expected to improve tolerability and adherence without compromising efficacy.
Conclusion
The NATALEE trial represents a significant step forward in addressing the unmet needs of HR+/HER2− EBC patients. By evaluating the efficacy and safety of ribociclib plus ET in a broad patient population, the trial has the potential to provide an additional treatment option for reducing both early and late recurrences in EBC.
