US Food and Drug Administration Approval Summary: Ribociclib With an Aromatase Inhibitor in the Adjuvant Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Stage II and III High-Risk Early Breast Cancer Treatment Setting
Abstract
PURPOSE On September 17, 2024, the US Food and Drug Administration (FDA) approved ribociclib in combination with an aromatase inhibitor (AI) for the adjuvant treatment of adults with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative stage II and III early breast cancer (EBC) who are at high risk of recurrence. PATIENTS AND METHODS The FDA approval was based on NATALEE, a randomized (1:1), open-label, multicenter, multinational trial in adults of any sex or menopausal status with hormone receptor–positive, HER2-negative stage II and III EBC who received ribociclib plus an AI (Ribo + AI, n = 2,549) versus an AI (n = 2,552); patients also received goserelin as clinically indicated. Ribociclib was given at 400 mg once daily (3 weeks on/1 week off) for up to 36 months. AI was given per standard of care for at least 5 years. The primary end point was invasive disease-free survival (iDFS), defined according to Standardized Definitions for Efficacy End Points version 1.0 criteria. Overall survival (OS) was a secondary end point. RESULTS iDFS was statistically significant at the third interim analysis (IA3; January 2023; hazard ratio [HR], 0.75 [95% CI, 0.62 to 0.91]) in the intent-to treat (ITT) population. However, at IA3, there was a large amount of censoring for iDFS as only 20% of patients had completed 3 years of adjuvant therapy and OS was immature. Because of these concerns, FDA requested that NATALEE continue until the final iDFS analysis. At the final iDFS analysis, the iDFS at 36 months was 90.7% (95% CI, 89.3 to 91.8) for Ribo + AI versus 87.6% (95% CI, 86.1 to 88.9) for AI, with a HR of 0.75 (95% CI, 0.63 to 0.89). More patients who received ribociclib experienced all-grade (98% Ribo + AI v 88% AI) and grade ≥3 (64% Ribo + AI v 19% AI) adverse reactions (ARs). CONCLUSION Addition of adjuvant ribociclib to NSAI for adults with high-risk stage II and III hormone receptor–positive, HER2-negative EBC demonstrated a favorable benefit-risk profile with a statistically significant iDFS advantage. OS data remain immature.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (39)
Jennifer J. Gao
US Food and Drug Administration, Silver Spring, MD
Tatiana M. Prowell
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD
Haley Gittleman
US Food and Drug Administration, Silver Spring, MD
Joyce Cheng
Mallorie Fiero
US Food and Drug Administration, Silver Spring, MD
Ilynn Bulatao
1FDA, Silver Spring, United States
George Ching-Jey Chang
US Food and Drug Administration, Silver Spring, MD
Tiffany K. Ricks
US Food and Drug Administration, Silver Spring, MD
Francis Green
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Huali Wu
Jingyu Yu
US Food and Drug Administration, Silver Spring, MD
Manuela Grimstein
US Food and Drug Administration, Silver Spring, MD
Yuching Yang
US Food and Drug Administration, Silver Spring, MD
Hong Zhao
Qi Liu
Rohit Kolhatkar
US Food and Drug Administration, Silver Spring, MD
Tingting Gao
Chi-Ming Tu
US Food and Drug Administration, Silver Spring, MD
Sherry Hou
US Food and Drug Administration, Silver Spring, MD
Susan Redwood
US Food and Drug Administration, Silver Spring, MD
Barbara Fuller
US Food and Drug Administration, Silver Spring, MD
LaShawn Griffiths
US Food and Drug Administration, Silver Spring, MD
Mispa Ajua-Alemanji
US Food and Drug Administration, Silver Spring, MD
Courtney Leach
US Food and Drug Administration, Silver Spring, MD
Stacie Woods
US Food and Drug Administration, Silver Spring, MD
Oladimeji Akinboro
United States Food and Drug Administration - Center for Drug Evaluation and Research, Office of New Drugs, Office of Oncologic Diseases, Silver Spring, MD
Preeti Narayan
US Food and Drug Administration, Silver Spring, MD
Mirat Shah
Office of Oncologic Diseases, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
Christy Osgood
US Food and Drug Administration, Silver Spring, MD
Ramesh Raghavachari
US Food and Drug Administration, Silver Spring, MD
Atiqur Rahman
US Food and Drug Administration, Silver Spring, MD
Shenghui Tang
US Food and Drug Administration, Silver Spring, MD
Vishal Bhatnagar
Nicole Gormley
US Food and Drug Administration, Silver Spring, MD
Tamy Kim
US Food and Drug Administration, Silver Spring, MD
William F. Pierce
US Food and Drug Administration, Silver Spring, MD
Richard Pazdur
From the Oncology Center of Excellence (G.U.M., R.P.) and the Office of the Commissioner (N.N.B., R.M.C.), Food and Drug Administration, Silver Spring, MD.
Paul G. Kluetz
Laleh Amiri-Kordestani