Adding ribociclib to first-line treatment with letrozole improves overall survival (OS) in postmenopausal patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, a phase 3 trial suggests.1

These results, from the MONALEESA-2 trial, were published in The New England Journal of Medicine.

MONALEESA-2 ( Identifier: NCT01958021) included 668 postmenopausal patients with HR+, HER2- advanced breast cancer. They were randomly assigned to receive letrozole plus ribociclib (n=334) or letrozole plus placebo (n=334).

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Prior results from the trial showed significantly longer progression-free survival (PFS) with ribociclib. At a median follow-up of 26.4 months, the median PFS was 25.3 months with ribociclib and 16.0 months with placebo (hazard ratio, 0.57; 95% CI, 0.46 to 0.70; P <.001).2

In the current analysis, the median follow-up was 6.6 years.1 The median duration of trial treatment was 20.2 months in the ribociclib arm and 14.1 months in the placebo arm. Of the patients who discontinued trial treatment, 87.8% in the ribociclib arm and 90.2% in the placebo arm received subsequent antineoplastic therapies.

At last follow-up, 181 patients (54.2%) in the ribociclib arm and 219 patients (65.6%) in the placebo arm had died.

The median OS was 63.9 months with ribociclib and 51.4 months with placebo (hazard ratio, 0.76; 95% CI, 0.63-0.93; P = .008). The 48-month OS rate was 60.9% and 55.2%, respectively. At 72 months, the OS rate was 44.2% and 32.0%, respectively.

Adverse events in this analysis were consistent with previously reported results, according to the researchers. Grade 3-4 adverse events of special interest (in the ribociclib and placebo arms, respectively) were neutropenia (63.8% vs 1.2%), hepatobiliary toxic effects (14.4% vs 4.8%), and prolonged QT interval (4.5% vs 2.1%).

“This analysis of the MONALEESA-2 trial showed a significant and clinically meaningful difference in overall survival of 12.5 months with first-line ribociclib plus letrozole as compared with placebo plus letrozole in postmenopausal patients with advanced HR-positive, HER2-negative breast cancer, with a 24% relative reduction in the risk of death,” the researchers concluded.

Disclosures: This research was supported by Novartis. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


  1. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. Published online March 10, 2022. doi:10.1056/NEJMoa2114663
  2. Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phase III trial of firstline ribociclib plus letrozole versus placebo plus letrozole in hormone receptor positive, HER2-negative advanced breast cancer. Ann Oncol. 2018; 29: 1541-7. doi:10.1093/annonc/mdz215