Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2− Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial
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Abstract
Purpose: Ribociclib plus endocrine therapy (ET) demonstrated a statistically significant progression-free survival and overall survival (OS) benefit in the phase III MONALEESA-7 trial of pre-/perimenopausal patients with hormone receptor (HR)-positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC). The median OS was not reached in the ribociclib arm in the protocol-specified final analysis; we hence performed an exploratory OS and additional outcomes analysis with an extended follow-up (median, 53.5 months). Patients and Methods: Patients were randomized to receive ET [goserelin plus nonsteroidal aromatase inhibitor (NSAI) or tamoxifen] with ribociclib or placebo. OS was evaluated with a stratified Cox proportional hazard model and summarized with Kaplan–Meier methods. Results: The intent-to-treat population included 672 patients. Median OS was 58.7 months with ribociclib versus 48.0 months with placebo [hazard ratio = 0.76; 95% confidence interval (CI), 0.61–0.96]. Kaplan–Meier estimated OS at 48 months was 60% and 50% with ribociclib and placebo, respectively. Subgroup analyses were generally consistent with the OS benefit, including patients who received NSAI and patients aged less than 40 years. Subsequent antineoplastic therapies following discontinuation were balanced between the ribociclib (77%) and placebo (78%) groups. Use of cyclin-dependent kinase 4/6 inhibitors after discontinuation was higher with placebo (26%) versus ribociclib (13%). Time to first chemotherapy was significantly delayed with ribociclib versus placebo. No drug–drug interactions were observed between ribociclib and either NSAI. Conclusions: Ribociclib plus ET continued to show significantly longer OS than ET alone in pre-/perimenopausal patients, including patients aged less than 40 years, with HR+/HER2− ABC with 53.5 months of median follow-up (ClinicalTrials.gov, NCT02278120).
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In MONALEESA-7, a significant overall survival benefit was observed with first-line ribociclib + NSAI versus NSAI alone in pre/perimenopausal women, with median overall survival not reached vs 40.7 months (HR 0.70; 95% CI 0.50-0.98); an exploratory extended follow-up reported median overall survival 58.7 vs 47.7 months (HR 0.798; 95% CI 0.62-1.04).
“In MONALEESA-7, a significant OS benefit was observed with first-line ribociclib + NSAI versus NSAI alone (mOS, not reached [NR] vs. 40.7 months [HR 0.70; 95% CI 0.50–0.98]) in pre/perimenopausal women; in addition, an exploratory analysis with extended follow-up reported an mOS of 58.7 versus 47.7 for ribociclib + NSAI versus NSAI alone (HR 0.798; 95% CI 0.62–1.04) [15, 16].”
From Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2- advanced breast cancer receiving first-line ribociclib plus fulvestrant. (2023) · cites this paper as [16]
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Experimental — accuracy not yet measuredThis is the third pivotal trial to demonstrate a significant improvement in overall survival with ribociclib in a first-line setting.
“This is the third pivotal trial to demonstrate a significant improvement in OS with ribociclib in a first-line setting”
From Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2- advanced breast cancer receiving first-line ribociclib plus fulvestrant. (2023) · cites this paper as [16]
The Introduction and Discussion report a significant overall-survival benefit with first-line ribociclib in MONALEESA-7. They do not establish that the trial described in the citing sentence was the third pivotal trial to show this benefit; the Discussion instead describes MONALEESA-7 as the first CDK4/6-inhibitor trial to demonstrate a statistically significant overall-survival benefit. Page numbers were not available in our copy. (LLM, conf=0.86)
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Cited by
Sorted by citations
Neven, P., Fasching, P. A., Chia, S., Jerusalem, G., De Laurentiis, M., Im, S.-A., Petrakova, K., Bianchi, G. V., Martín, M., Nusch, A., et al. (2023) · Breast Cancer Research · doi:10.1186/s13058-023-01701-9 · Cited by 83 · see citing works
“While all MONALEESA studies allowed patients treated in the first line, patients with early relapse were included for analysis in the second-line population of MONALEESA-3 and in the first-line population of MONALEESA-2/7 [14, 16, 17].”
BackgroundSelf-citation
- Authors
- Lu, Y.-S., Im, S.-A., Colleoni, M., Franke, F., Bardia, A., Cardoso, F., Harbeck, N., Hurvitz, S., Chow, L., Sohn, J., Lee, K. S., Campos-Gomez, S., Villanueva Vazquez, R., Jung, K. H., Babu, K. G., Wheatley-Price, P., De Laurentiis, M., Im, Y.-H., Kuemmel, S., El-Saghir, N., O'Regan, R., Gasch, C., Solovieff, N., Wang, C., Wang, Y., Chakravartty, A., Ji, Y., & Tripathy, D.
- Affiliations
- National Taiwan University (TW)
- Seoul National University (KR)
- European Institute of Oncology (IT)
- 4Hospital de Caridade de Ijuí, CACON, Ijuí, Brazil.
- Harvard University (US)
- Champalimaud Foundation (PT)
- Ludwig-Maximilians-Universität München (DE)
- University of California, Los Angeles (US)
- 9Organisation for Oncology and Translational Research, Hong Kong.
- Severance Hospital (KR)
- National Cancer Center (KR)
- 12Centro Oncológico Estatal, Instituto de Seguridad Social del Estado de México y Municipios, Toluca, Mexico.
- 13Institut Català d'Oncologia, Hospital Moisès Broggi, Barcelona, Spain.
- Asan Medical Center (KR)
- Kidwai Memorial Institute of Oncology (IN)
- University of Ottawa (CA)
- 17Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.
- Samsung Medical Center (KR)
- Kliniken Essen-Mitte (DE)
- American University of Beirut Medical Center (LB)
- University of Wisconsin–Madison (US)
- 23Novartis Ireland Limited, Dublin, Ireland.
- Novartis (Switzerland) (CH)
- 26Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Lu, Yen-Shen
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2021-12-27
- Volume
- 28
- Issue
- 5
- Pages
- 851-859
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC9377723
- OpenAlex
- W4200069316
- Cited by
- 287
- References
- 5
- Citations by year
- 2026: 51 · 2025: 91 · 2024: 73 · 2023: 56 · 2022: 16
- FWCI
- 23.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Cancer Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Novartis Pharmaceuticals Corporation (N/A)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- ribociclib, endocrine therapy, hormone receptor-positive HER2-negative breast cancer, advanced breast cancer, premenopausal women, overall survival, cyclin-dependent kinase 4/6 inhibitors, goserelin, nonsteroidal aromatase inhibitors, tamoxifen, drug-drug interactions
- MeSH terms
- Aminopyridines, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Female, Humans, Purines, Receptors, Estrogen, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Aromatase Inhibitors, Perimenopause
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