Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2− advanced breast cancer receiving first-line ribociclib plus fulvestrant

Breast Cancer Research - Tập 25 Số 1
Patrick Neven1, PA Fasching2, Stephen Chia3, Guy Jérusalem4, Michelino De Laurentiis5, Seock‐Ah Im6, Katarína Petráková7, Giulia Bianchi8, M. Martín9, Arnd Nusch10, Gabe S. Sonke11, Luis de la Cruz-Merino12, J. Thaddeus Beck13, Juan Pablo Zarate14, Y. Wang14, Arunava Chakravartty14, C. Wang15, Dennis J. Slamon16
1Multidisciplinary Breast Centre, Universitair Ziekenhuis Leuven, Leuven, Belgium
2University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
3British Columbia Cancer Agency, Vancouver, Canada
4CHU Liege and Liège University, Liège, Belgium
5Istituto Nazionale Tumori – IRCCS – Fondazione “G. Pascale”, Naples, Italy
6Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
7Masaryk Memorial Cancer Institute, Brno, Czech Republic
8Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy
9Instituto 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
10Practice for Hematology and Internal Oncology, Velbert, Germany
11Netherlands Cancer Institute/Borstkanker Onderzoek Groep Study Center, Amsterdam, The Netherlands
12Hospital Universitario Virgen Macarena, Seville, Spain
13Highlands Oncology, Springdale, USA
14Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
15Novartis Pharma AG, Basel, Switzerland
16David Geffen School of Medicine at UCLA, Los Angeles, USA

Tóm tắt

Abstract 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.

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Breast Cancer Research

Tập 25 Số 1

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