Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2018 Feb;168(1):127-134.
doi: 10.1007/s10549-017-4518-8. Epub 2017 Nov 21.

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial

Joyce O'Shaughnessy  1 , Katarina Petrakova  2 , Gabe S Sonke  3 , Pierfranco Conte  4 , Carlos L Arteaga  5 , David A Cameron  6 , Lowell L Hart  7 , Cristian Villanueva  8 , Erik Jakobsen  9 , Joseph T Beck  10 , Deborah Lindquist  11 , Farida Souami  12 , Shoubhik Mondal  13 , Caroline Germa  13 , Gabriel N Hortobagyi  14
Affiliations
Clinical Trial

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial

Joyce O'Shaughnessy et al. Breast Cancer Res Treat. 2018 Feb.

Abstract

Purpose: Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer.

Methods: Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate.

Results: Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population.

Conclusions: Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

Keywords: Breast cancer; CDK inhibitor; De novo advanced breast cancer; Endocrine therapy; Hormone receptor-positive; Ribociclib.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

Dr. O’Shaughnessy reports advisory board member fees from Novartis. Dr. Sonke reports institutional reimbursement for steering committee activities and patient inclusion from Novartis during the conduct of the study. Dr. Cameron reports institutional reimbursement for consultancy from Novartis, Pfizer, and Lilly, outside the submitted work. Dr. Beck reports being the Principal Investigator of the CLEE011A2301 trial at Highlands Oncology Group. Dr. Souami and Dr. Germa are employees of Novartis Pharmaceuticals Corporation and hold Novartis stock options. Dr. Mondal is an employee of Novartis Pharmaceuticals Corporation. Dr. Hortobagyi reports personal fees from Novartis Pharmaceuticals Corporation during the conduct of the study; personal consultancy fees from Novartis Pharmaceuticals Corporation, Lilly USA LLC, Peregrine Pharmaceuticals Inc, F. Hoffmann-La Roche, Ltd. (Roche), Merck & Co, and Celgene Corp outside the submitted work; and personal Scientific/Advisory Committee Member fees from Pfizer Inc., F. Hoffmann-La Roche, Ltd. (Roche), Bayer HealthCare Pharmaceuticals, and Antigen Express outside the submitted work. Dr. Petrakova, Prof. Conte, Dr. Arteaga, Dr. Hart, Dr. Villanueva, Dr. Jakobsen, and Dr. Lindquist have nothing to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
MONALEESA-2 trial profile (CONSORT diagram)
Fig. 2
Fig. 2
Kaplan–Meier analysis of locally assessed progression-free survival in patients with de novo advanced breast cancer in the MONALEESA-2 trial. CI confidence interval
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. International Agency for Research on Cancer (2012) GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr/Default.aspx. Accessed 11 July 2017
    1. Hosford SR, Miller TW. Clinical potential of novel therapeutic targets in breast cancer: CDK4/6, src, JAK/STAT, PARP, HDAC, and PI3K/AKT/mTOR pathways. Pharmgenom Pers Med. 2014;7:203–215. - PMC - PubMed
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29. doi: 10.3322/caac.21254. - DOI - PubMed
    1. Miao H, Hartman M, Bhoo-Pathy N, et al. Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study. PLOS ONE. 2014;9:e93755. doi: 10.1371/journal.pone.0093755. - DOI - PMC - PubMed
    1. Cardoso F, Costa A, Senkus E, et al. 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3) Ann Oncol. 2017;28:16–33. doi: 10.1093/annonc/mdx447. - DOI - PMC - PubMed

Publication types

MeSH terms