# Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer

Source: https://onco.cc/key-papers/paper-monaleesa-2-n-engl-j-med-2016/  
OnCo record `paper-monaleesa-2-n-engl-j-med-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the MONALEESA-2 trial registered as NCT01958021, in New England Journal of Medicine (2016), chosen as the most cited paper whose own text cites the registry id.

## Summary

Background: The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2).

Methods: In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10 -5.

Results: The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10 -6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%, respectively.

Conclusions: Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021.).

Indexed on Europe PMC as PubMed record 27717303 (DOI 10.1056/nejmoa1609709). Its abstract cites the registry id NCT01958021, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: New England Journal of Medicine
- Year: 2016
- DOI: 10.1056/nejmoa1609709
- Authors: Hortobagyi GN, Stemmer SM, Burris HA, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT01958021 with the most citations, so it is the natural first reading for anyone following the MONALEESA-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- N Engl J Med 2016: https://doi.org/10.1056/nejmoa1609709
- PubMed: https://pubmed.ncbi.nlm.nih.gov/27717303/
- Europe PMC: https://europepmc.org/article/MED/27717303
- ClinicalTrials.gov NCT01958021: https://clinicaltrials.gov/study/NCT01958021

## Connected records

- trials: [MONALEESA-2](https://onco.cc/trials/monaleesa-2/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- ideas: [CDK4-selective inhibitors as the new first-line backbone](https://onco.cc/ideas/idea-cdk4-selective-first-line/)

---
JSON: https://onco.cc/api/v1/entities/paper-monaleesa-2-n-engl-j-med-2016.json