As reported in The New England Journal of Medicine by Dennis J. Slamon, MD, PhD, and colleagues, in the phase III MONALEESA-3 trial, the second interim analysis of overall survival has shown a significant benefit with the addition of ribociclib to fulvestrant in first- or second-line treatment of postmenopausal patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Dennis J. Slamon, MD, PhD

In the previously reported primary analysis of the trial, the addition of ribociclib to fulvestrant resulted in significantly longer progression-free survival (median = 20.5 vs 12.8 months, hazard ratio [HR] = 0.59, P <.001). Data on overall survival, a secondary endpoint, were not mature at the time of primary analysis.

Study Details

In the double-blind trial, 726 patients with advanced disease were randomly assigned 2:1 between June 2015 and June 2016 to receive 600 mg of oral ribociclib once daily for 21 consecutive days followed by 7 days off (n = 484) or placebo (n = 242), with all patients receiving 500 mg of intramuscular fulvestrant on day 1 of each 28-day cycle with an additional dose on day 15 of cycle 1. The study regimens were given as first- or second-line treatment for advanced disease.

Overall Survival

At the prespecified second interim analysis, at median follow-up of 39.4 months, estimated  overall survival at 42 months was 57.8% (95% confidence interval [CI] = 52.0%–63.2%) in the ribociclib group vs 45.9% (95% CI = 36.9%–54.5%) in the placebo group (HR = 0.72, P = .00455). In subgroup analysis, estimated overall survival at 42 months was 66.9% among the 237 ribociclib group patients vs 56.3% among the 128 placebo group patients who received first-line therapy (HR = 0.70, 95% CI = 0.48–1.02). Among the 237 patients in the ribociclib group and 109 patients in the placebo group receiving study therapy as second-line treatment, median overall survival was 40.2 months vs 32.5 months (HR = 0.73, 95% CI = 0.53–1.00).

Subsequent antineoplastic therapy was received by 81.5% of the ribociclib group and 84.7% of the placebo group; subsequent cyclin-dependent kinase 4/6 inhibitor treatment (including palbociclib, abemaciclib, and ribociclib) was received by 11.0% and 25.4% of patients, respectively.

In a descriptive update of progression-free survival, median durations were 33.6 months in the ribociclib group and 19.2 months in the placebo group among patients receiving first-line treatment. Among patients receiving study therapy as second-line treatment or who had early relapse (ie, relapse within 12 months after completion of adjuvant or neoadjuvant endocrine therapy), median progression-free survival was 14.6 vs 9.1 months.  

The investigators concluded, “Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant in patients with hormone receptor–positive, HER2-negative advanced breast cancer.”

Disclosure: The study was funded by Novartis. For full disclosures of the study authors, visit nejm.org.