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.
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.
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.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.