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.

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).

• Authors: Yen-Shen Lu, Seock-Ah Im, Marco Colleoni, Fabio Franke, Aditya Bardia, Fatima Cardoso, Nadia Harbeck, Sara Hurvitz, Louis Chow, Joohyuk Sohn, Keun Seok Lee, Saul Campos-Gomez, Rafael Villanueva Vazquez, Kyung Hae Jung, K Govind Babu, Paul Wheatley-Price, Michelino De Laurentiis, Young-Hyuck Im, Sherko Kuemmel, Nagi El-Saghir, Ruth O'Regan, Claudia Gasch, Nadia Solovieff, Craig Wang, Yongyu Wang, Arunava Chakravartty, Yan Ji, Debu Tripathy
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 5 Pg. 851-859 (Mar 01 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 34965945 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Aminopyridines
• Aromatase Inhibitors
• Purines
• Receptors, Estrogen
• Receptor, ErbB-2
• ribociclib

Topics

• Aminopyridines
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Aromatase Inhibitors
• Breast Neoplasms (drug therapy)
• Female
• Humans
• Perimenopause
• Purines
• Receptor, ErbB-2 (therapeutic use)
• Receptors, Estrogen