Addition of Ribociclib to Fulvestrant Improves Progression-Free Survival in HR-Positive, HER2-Negative Advanced Breast Cancer


Key Points

  • The addition of ribociclib to fulvestrant significantly improved progression-free survival.
  • Benefits were similar among patients who were treatment-naive or had received up to one line of endocrine therapy in the advanced setting. 

As reported by Slamon and colleagues in the Journal of Clinical Oncology, the phase III MONALEESA-3 trial has shown significant improvement in progression-free survival with the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to fulvestrant (Faslodex) in hormone receptor (HR)-positive, HER2-negative advanced breast cancer.

Study Details

In the double-blind trial, 726 postmenopausal women who were treatment-naive or had received up to one line of prior endocrine therapy for advanced disease from 177 sites in 27 countries were randomized 2:1 between June 2015 and June 2016 to receive ribociclib plus fulvestrant (n = 484) or placebo plus fulvestrant (n = 242). Treatment consisted of oral ribociclib at 600 mg/d for 3 weeks on and 1 week off and intramuscular fulvestrant at 500 mg on day 1 of each 28-day cycle, with an additional dose on day 15 of cycle 1. The primary endpoint was locally assessed progression-free survival.

Median time from randomization to data cutoff was 20.4 months. Among all patients, median progression-free survival was 20.5 months in the ribociclib/fulvestrant group vs 12.8 months in the fulvestrant/placebo group (hazard ratio [HR] = 0.593, P < .001). Consistent benefit was observed among the 238 and 129 patients who were treatment-naive (HR = 0.577, 95% confidence interval [CI] = 0.415–0.802) and among the 236 and 109 patients who had received up to one line of prior endocrine therapy (HR = 0.565, 95% CI = 0.428–0.744).

Among patients with measurable disease at baseline, the overall response rate was 40.9% vs 28.7% (P = .003). At first interim analysis, overall survival data were immature. At the time of analysis, death had occurred in 14.5% vs 20.7% of patients, with results not crossing the prespecified O’Brien-Fleming stopping boundary.

Adverse Events

Grade 3 adverse events reported in at least 10% of patients in either the ribociclib/fulvestrant group or fulvestrant/placebo group were neutropenia (46.6% vs 0%) and leukopenia (13.5% vs 0%), with neutropenia (6.8% vs 0%) being the only grade 4 adverse event reported in at least 5% of patients. Serious adverse events occurred in 28.6% vs 16.6% of patients, with the most common events being pneumonia (1.9% vs 0%) and dyspnea (1.2% vs 2.1%). One death in the ribociclib-plus-fulvestrant group—due to acute respiratory distress syndrome in a patient with baseline lung metastases—was considered possibly related to study treatment.

The investigators concluded, “Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer.”

The study was supported by Novartis Pharmaceuticals.

Dennis J. Slamon, MD, PhD, of UCLA Medical Center, is the corresponding author for the Journal of Clinical Oncology article.

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®.