Safety and treatment duration of ribociclib + nonsteroidal aromatase inhibitor in HR+/HER2- early breast cancer: a phase 3 randomized controlled trial (NATALEE).
16 affiliations
- 1Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
- 2Breast Center, Department of Obstetrics and Gynecology and CCC Munich, LMU University Hospital, Munich, Germany.
- 3Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- 4Texas Oncology, Baylor University Medical Center and the US Oncology Research Network, Dallas, TX, USA.
- 5National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City, Taiwan.
- 6Centro de Investigación Biomédica en Red de Cáncer, Grupo Español de Investigación en Cáncer de Mama, Instituto de Investigación Sanitaria Gregorio Marañon, Universidad Complutense, Madrid, Spain.
- 7Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
- 8Department of Medical Oncology, Gustave Roussy, Villejuif, France.
- 9Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing, China.
- 10Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy.
- 11Interdisciplinary Breast Cancer Center, Helios Klinikum Berlin-Buch, Berlin, Germany.
- 12Translational Research in Oncology (TRIO), Paris, France.
- 13Novartis Pharma AG, Basel, Switzerland.
- 14Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
- 15Novartis Ireland, Dublin, Ireland.
- 16Grupo Oncoclínicas, Centro de Pesquisa em Oncologia, Hospital São Lucas, PUCRS, Latin American Cooperative Oncology Group (LACOG), Coroados 837, Porto Alegre, RS, 9190580, Brazil. [email protected].
Abstract
Background
The phase 3 NATALEE trial demonstrated sustained invasive disease-free survival benefit for patients with stage II or III HR+/HER2- early breast cancer (EBC) treated with ribociclib + nonsteroidal aromatase inhibitor (NSAI) vs. NSAI alone. Here we report detailed safety and tolerability data from NATALEE to further inform clinical decision-making.Methods
In NATALEE, men and pre- and postmenopausal women with HR+/HER2- EBC were randomized 1:1 to ribociclib 400 mg/day (3 weeks on/1 week off; 36 months) + NSAI (anastrozole or letrozole; ≥60 months) or NSAI alone. Men and premenopausal women also received goserelin. Safety analyses included incidence of treatment-emergent adverse events (AEs) as well as severity, timing, management, and outcomes. Safety parameters among older vs. younger patients were also assessed.Results
At this 45.7-month median follow-up (data cutoff: April 29, 2024), the safety analysis set comprised 4967 patients receiving ribociclib + NSAI (n = 2526) or NSAI alone (n = 2441). The most common grade ≥ 3 AEs occurring with ribociclib + NSAI vs. NSAI alone, respectively, were neutropenia (grouped term; 44.4% vs. 0.9%), liver-related AEs (grouped term; 8.6% vs. 1.7%), and leukopenia (grouped term; 8.0% vs. 0.4%). Drug-related serious AEs occurred in 2.8% vs. 0.5%, respectively. Among patients receiving ribociclib + NSAI, AE-related ribociclib discontinuation occurred in 20.2% (median onset, 4.3 months), with 9.0% of instances occurring because of liver-related AEs. AE-related ribociclib dose interruptions (66.8%; median onset, 1.8 months) and dose reductions (23.0%; median onset, 3.2 months) were primarily driven by neutropenia (dose interruptions, 43.4%; dose reductions, 14.1%). In the ribociclib + NSAI arm, AE incidence and ribociclib dose interruptions or reductions occurred at similar rates among older patients (≥ 65 years) and younger patients (< 65 years). A higher proportion of older patients permanently discontinued ribociclib due to AEs (28.1%; n = 113/402) vs. younger patients (18.6%; n = 396/2124), most commonly due to alanine aminotransferase increased (older, 8.5%; younger, 7.0%).Conclusions
Overall, ribociclib 400 mg was well tolerated, including in older patients, and AEs were manageable with current NATALEE label recommendations of dose interruptions and reductions. Trial registration ClinicalTrials.gov identifier: NCT03701334 (registered September 21, 2018).
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BibTeX
@article{rugo2026safety,
title = {{Safety and treatment duration of ribociclib + nonsteroidal aromatase inhibitor in HR+/HER2- early breast cancer: a phase 3 randomized controlled trial (NATALEE).}},
author = {H S Rugo and N Harbeck and G N Hortobagyi and J O'Shaughnessy and C-S Huang and M Martin and D Juric and B Pistilli and B Xu and M De Laurentiis and M Untch and K Afenjar and M Gao and Z Li and N Bolotova and S Waters and C Barrios},
journal = {Breast cancer research : BCR},
year = {2026},
month = aug,
doi = {10.1186/s13058-026-02352-2},
url = {https://europepmc.org/article/MED/42968162},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Safety and treatment duration of ribociclib + nonsteroidal aromatase inhibitor in HR+/HER2- early breast cancer: a phase 3 randomized controlled trial (NATALEE).
AU - H S Rugo
AU - N Harbeck
AU - G N Hortobagyi
AU - J O'Shaughnessy
AU - C-S Huang
AU - M Martin
AU - D Juric
AU - B Pistilli
AU - B Xu
AU - M De Laurentiis
AU - M Untch
AU - K Afenjar
AU - M Gao
AU - Z Li
AU - N Bolotova
AU - S Waters
AU - C Barrios
PY - 2026
DA - 2026/08/01
JO - Breast cancer research : BCR
DO - 10.1186/s13058-026-02352-2
UR - https://europepmc.org/article/MED/42968162
AB - Background The phase 3 NATALEE trial demonstrated sustained invasive disease-free survival benefit for patients with stage II or III HR+/HER2- early breast cancer (EBC) treated with ribociclib + nonsteroidal aromatase inhibitor (NSAI) vs. NSAI alone. Here we report detailed safety and tolerability data from NATALEE to further inform clinical decision-making.Methods In NATALEE, men and pre- and postmenopausal women with HR+/HER2- EBC were randomized 1:1 to ribociclib 400 mg/day (3 weeks on/1 week off; 36 months) + NSAI (anastrozole or letrozole; ≥60 months) or NSAI alone. Men and premenopausal women also received goserelin. Safety analyses included incidence of treatment-emergent adverse events (AEs) as well as severity, timing, management, and outcomes. Safety parameters among older vs. younger patients were also assessed.Results At this 45.7-month median follow-up (data cutoff: April 29, 2024), the safety analysis set comprised 4967 patients receiving ribociclib + NSAI (n = 2526) or NSAI alone (n = 2441). The most common grade ≥ 3 AEs occurring with ribociclib + NSAI vs. NSAI alone, respectively, were neutropenia (grouped term; 44.4% vs. 0.9%), liver-related AEs (grouped term; 8.6% vs. 1.7%), and leukopenia (grouped term; 8.0% vs. 0.4%). Drug-related serious AEs occurred in 2.8% vs. 0.5%, respectively. Among patients receiving ribociclib + NSAI, AE-related ribociclib discontinuation occurred in 20.2% (median onset, 4.3 months), with 9.0% of instances occurring because of liver-related AEs. AE-related ribociclib dose interruptions (66.8%; median onset, 1.8 months) and dose reductions (23.0%; median onset, 3.2 months) were primarily driven by neutropenia (dose interruptions, 43.4%; dose reductions, 14.1%). In the ribociclib + NSAI arm, AE incidence and ribociclib dose interruptions or reductions occurred at similar rates among older patients (≥ 65 years) and younger patients (< 65 years). A higher proportion of older patients permanently discontinued ribociclib due to AEs (28.1%; n = 113/402) vs. younger patients (18.6%; n = 396/2124), most commonly due to alanine aminotransferase increased (older, 8.5%; younger, 7.0%).Conclusions Overall, ribociclib 400 mg was well tolerated, including in older patients, and AEs were manageable with current NATALEE label recommendations of dose interruptions and reductions. Trial registration ClinicalTrials.gov identifier: NCT03701334 (registered September 21, 2018).
SN - 1465-5411
SN - 1465-542X
ER -