{ "abstract": "Background\n\nThe 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\n\nIn 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\n\nAt 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\n\nOverall, 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).", "abstract_shown": true, "affiliations": [ "Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.", "Breast Center, Department of Obstetrics and Gynecology and CCC Munich, LMU University Hospital, Munich, Germany.", "Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.", "Texas Oncology, Baylor University Medical Center and the US Oncology Research Network, Dallas, TX, USA.", "National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City, Taiwan.", "Centro 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.", "Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.", "Department of Medical Oncology, Gustave Roussy, Villejuif, France.", "Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing, China.", "Istituto Nazionale Tumori IRCCS \"Fondazione G. Pascale\", Naples, Italy.", "Interdisciplinary Breast Cancer Center, Helios Klinikum Berlin-Buch, Berlin, Germany.", "Translational Research in Oncology (TRIO), Paris, France.", "Novartis Pharma AG, Basel, Switzerland.", "Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.", "Novartis Ireland, Dublin, Ireland.", "Grupo Oncoclínicas, Centro de Pesquisa em Oncologia, Hospital São Lucas, PUCRS, Latin American Cooperative Oncology Group (LACOG), Coroados 837, Porto Alegre, RS, 9190580, Brazil. barrios@thummi.global." ], "article_type": "research article", "arxiv": null, "author_total": 17, "authors": [ { "affs": [ 0 ], "name": "H S Rugo" }, { "affs": [ 1 ], "name": "N Harbeck" }, { "affs": [ 2 ], "name": "G N Hortobagyi" }, { "affs": [ 3 ], "name": "J O'Shaughnessy" }, { "affs": [ 4 ], "name": "C-S Huang" }, { "affs": [ 5 ], "name": "M Martin" }, { "affs": [ 6 ], "name": "D Juric" }, { "affs": [ 7 ], "name": "B Pistilli" }, { "affs": [ 8 ], "name": "B Xu" }, { "affs": [ 9 ], "name": "M De Laurentiis" }, { "affs": [ 10 ], "name": "M Untch" }, { "affs": [ 11 ], "name": "K Afenjar" }, { "affs": [ 12 ], "name": "M Gao" }, { "affs": [ 13 ], "name": "Z Li" }, { "affs": [ 12 ], "name": "N Bolotova" }, { "affs": [ 14 ], "name": "S Waters" }, { "affs": [ 15 ], "name": "C Barrios" } ], "bibtex": "https://research.draconitic.com/paper/b9wfwx0ztj2b7.bib", "cited_by": 1, "doi": "10.1186/s13058-026-02352-2", "fulltext_url": "https://europepmc.org/articles/PMC13726065", "id": "b9wfwx0ztj2b7", "issns": [ "1465-5411", "1465-542X" ], "landing_url": "https://europepmc.org/article/MED/42968162", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Research" ], [ "lcc", "RC254-282" ], [ "openalex", "2740|Advanced Breast Cancer Therapies" ] ], "openalex": "W7172416469", "pdf_url": "https://europepmc.org/articles/PMC13726065?pdf=render", "pmcid": "PMC13726065", "pmid": "42968162", "published": "2026-08-01", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/b9wfwx0ztj2b7.ris", "sources": [ { "first_seen": "2026-11-03T15:20:54Z", "native_id": "MED:42968162", "source": "europepmc", "url": "https://europepmc.org/article/MED/42968162" }, { "first_seen": "2026-11-05T12:22:29Z", "native_id": "PMC13726065", "source": "pmc", "url": "https://doi.org/10.1186/s13058-026-02352-2" }, { "first_seen": "2026-11-08T14:21:03Z", "native_id": "0ea85ec544e641a2a1618ea2ac7ec016", "source": "doaj", "url": "https://doi.org/10.1186/s13058-026-02352-2" } ], "subjects": [ { "field": "medicine", "origin": "lcc:RC254-282", "subfield": "oncology" } ], "title": "Safety and treatment duration of ribociclib + nonsteroidal aromatase inhibitor in HR+/HER2- early breast cancer: a phase 3 randomized controlled trial (NATALEE).", "title_text": "Safety and treatment duration of ribociclib + nonsteroidal aromatase inhibitor in HR+/HER2- early breast cancer: a phase 3 randomized controlled trial (NATALEE).", "type": "peer-reviewed", "updated_at": "2026-11-09T14:21:23Z", "url": "https://research.draconitic.com/paper/b9wfwx0ztj2b7", "venue": "Breast cancer research : BCR", "versions": [] }