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.

British Columbia Cancer Agency Vancouver BC Canada

Cancer Research Institute Seoul National University Hospital Seoul National University College of Medicine Seoul Republic of Korea

CHU Liege and Liège University Liège Belgium

David Geffen School of Medicine at UCLA Los Angeles CA USA

Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori Milan Italy

Highlands Oncology Springdale AR USA

Hospital Universitario Virgen Macarena Seville Spain

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

Istituto Nazionale Tumori IRCCS Fondazione G Pascale Naples Italy

Masaryk Memorial Cancer Institute Brno Czech Republic

Multidisciplinary Breast Centre Universitair Ziekenhuis Leuven Herestraat 49 3000 Leuven Belgium

Netherlands Cancer Institute Borstkanker Onderzoek Groep Study Center Amsterdam The Netherlands

Novartis Pharma AG Basel Switzerland

Novartis Pharmaceuticals Corporation East Hanover NJ USA

Practice for Hematology and Internal Oncology Velbert Germany

University Hospital Erlangen Friedrich Alexander University Erlangen Nuremberg Erlangen Germany

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ClinicalTrials.gov
NCT02422615