Efficacy, safety, and patient-reported outcomes across young to older age groups of patients with HR+/HER2- advanced breast cancer treated with ribociclib plus endocrine therapy in the randomized MONALEESA-2, -3, and -7 trials

Lowell L Hart; Seock-Ah Im; Sara M Tolaney; Mario Campone; Timothy Pluard; Berta Sousa; Gilles Freyer; Thomas Decker; Kevin Kalinsky; Gary Sopher; Melissa Gao; Huilin Hu; Sherko Kuemmel

doi:10.1016/j.ejca.2025.115225

Efficacy, safety, and patient-reported outcomes across young to older age groups of patients with HR+/HER2- advanced breast cancer treated with ribociclib plus endocrine therapy in the randomized MONALEESA-2, -3, and -7 trials

Eur J Cancer. 2025 Jan 8:217:115225. doi: 10.1016/j.ejca.2025.115225. Online ahead of print.

Authors

Lowell L Hart¹, Seock-Ah Im², Sara M Tolaney³, Mario Campone⁴, Timothy Pluard⁵, Berta Sousa⁶, Gilles Freyer⁷, Thomas Decker⁸, Kevin Kalinsky⁹, Gary Sopher¹⁰, Melissa Gao¹¹, Huilin Hu¹⁰, Sherko Kuemmel¹²

Affiliations

¹ Florida Cancer Specialists, Sarah Cannon Research Institute, Fort Myers, FL, USA; Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address: llhart@wakehealth.edu.
² Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
³ Dana-Farber Cancer Institute, Boston, MA, USA.
⁴ Institut de Cancérologie de l'Ouest/René Gauducheau Centre de Recherche en Cancérologie, St. Herblain, France.
⁵ Saint Luke's Cancer Institute, Kansas City, MO, USA.
⁶ Breast Unit, Champalimaud Clinical and Research Center/Champalimaud Foundation, Lisbon, Portugal.
⁷ Oncology Department, Hôpital Lyon Sud, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL) and Université de Lyon, France.
⁸ Gemeinschaftspraxis für Hämatologie und Onkologie Ravensburg, Germany.
⁹ Winship Cancer Institute at Emory University, Atlanta, GA, USA.
¹⁰ Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
¹¹ Novartis Pharma AG, Basel, Switzerland.
¹² Department of Gynecology with Breast Unit, Charité Hospital Berlin, Germany; Interdisciplinary Breast Unit, Kliniken Essen Mitte, Essen, Germany.

PMID: 39826197
DOI: 10.1016/j.ejca.2025.115225

Abstract

Background: Ribociclib + endocrine therapy (ET) showed significant progression-free survival (PFS) and overall survival (OS) benefits in the MONALEESA trials in patients with HR+ /HER2 - advanced breast cancer (ABC). We report efficacy, safety, and patient-reported outcomes (PROs) across age groups, including older patients, in these trials.

Methods: Data from the MONALEESA-2, -3, and -7 trials for pre- and postmenopausal patients receiving first-line treatment for ABC were pooled and analyzed by age (<65y, 65-74y, and ≥75y). PFS, OS, time to first chemotherapy (TTC), and time to definitive deterioration (TTD) in PROs were evaluated using Kaplan-Meier methods; a Cox regression model stratified by study and liver/lung metastasis was used for hazard ratios.

Results: Among 1229 patients included, 63 % were < 65y, 27 % were 65-74y, and 10 % were ≥ 75y. Baseline characteristics were generally well balanced. Regardless of patient age, ribociclib+ET showed a consistent PFS and OS benefit and delayed TTC. With ribociclib+ET, the most common first subsequent treatment was ET. Safety results were consistent with those in the overall trial population; no new signals were identified. Rates of discontinuation due to AEs with ribociclib+ET were numerically higher in patients ≥ 75y. Among patients who discontinued treatment due to AEs, the percentage without prior dose reduction was higher in those ≥ 75y. A PRO benefit with ribociclib+ET was observed across all age groups for pain and fatigue scores.

Conclusions: This analysis demonstrated that ribociclib+ET is an effective and well-tolerated treatment for patients of all age groups with HR+ /HER2 - ABC, including older patients. (MONALEESA-2, NCT01958021; MONALEESA-3, NCT02422615; MONALEESA-7, NCT02278120).

Keywords: Age groups; Breast cancer; CDK4/6 inhibitors; Efficacy; Patient-reported outcomes; Safety.

Associated data

ClinicalTrials.gov/NCT02278120
ClinicalTrials.gov/NCT02422615