Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2- advanced breast cancer receiving first-line ribociclib plus fulvestrant.
Advanced breast cancer; CDK4/6 inhibitor; First line; Overall survival; Ribociclib; Fulvestrant; ribociclib; Humans; Female; Proportional Hazards Models; Postmenopause; Breast Neoplasms/drug therapy; Breast Neoplasms; Oncology; Cancer Research
Abstract :
[en] [en] BACKGROUND: The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2- ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population.
METHODS: Postmenopausal patients with HR+/HER2- ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan-Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615).
RESULTS: At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50-0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed.
CONCLUSIONS: This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2- ABC.
Disciplines :
Oncology
Author, co-author :
Neven, P; Multidisciplinary Breast Centre, Universitair Ziekenhuis Leuven, Herestraat 49, 3000, Leuven, Belgium. patrick.neven@uzleuven.be
Fasching, P A; University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
Chia, S; British Columbia Cancer Agency, Vancouver, BC, Canada
Jerusalem, Guy ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
De Laurentiis, M; Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy
Im, S-A; Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
Petrakova, K; Masaryk Memorial Cancer Institute, Brno, Czech Republic
Bianchi, G V; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy
Martín, M; Instituto de Investigación Sanitaria Gregorio Marañon, Centro de Investigación Biomédica en Red de Cáncer, Grupo Español de Investigación en Cáncer de Mama, Universidad Complutense, Madrid, Spain
Nusch, A; Practice for Hematology and Internal Oncology, Velbert, Germany
Sonke, G S; Netherlands Cancer Institute/Borstkanker Onderzoek Groep Study Center, Amsterdam, The Netherlands
De la Cruz-Merino, L; Hospital Universitario Virgen Macarena, Seville, Spain
Beck, J T; Highlands Oncology, Springdale, AR, USA
Zarate, J P; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Wang, Y; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Chakravartty, A; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Wang, C; Novartis Pharma AG, Basel, Switzerland
Slamon, D J; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2- advanced breast cancer receiving first-line ribociclib plus fulvestrant.
Publication date :
31 August 2023
Journal title :
Breast Cancer Research
ISSN :
1465-5411
eISSN :
1465-542X
Publisher :
BioMed Central Ltd, England
Volume :
25
Issue :
1
Pages :
103
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
The study was sponsored by Novartis. We thank the patients who participated in this trial, their families, and their caregivers; members of the data monitoring committee; members of the study steering committee; staff members who helped with the trial at each site; and Shashank Tandon, PhD, of MediTech Media for medical editorial assistance with this manuscript. Ribociclib was discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals.This work was supported by Novartis Pharmaceuticals Corporation. The funder of this study, in agreement with the authors and the study steering committee members, designed this study. Representatives of the trial sponsor performed data collection and the subsequent analysis.
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