Background: Ribociclib combined with an aromatase inhibitor has been shown to significantly prolong progression-free survival (PFS) in premenopausal1 and postmenopausal2 women with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) who had not been treated previously for ABC.
Objectives: This review highlights the available efficacy, safety, and patient-reported outcomes of ribociclib plus fulvestrant in patients with ABC who had received ≤1 line of prior endocrine therapy (ET).3,4
Methods: MONALEESA-3 (ClinicalTrials.gov identifier, NCT02422615) is a phase 3, double-blind trial of patients randomized 2:1 to receive daily ribociclib 600 mg (3 weeks on/1 week off) or placebo in combination with fulvestrant 500 mg (administered on the first day of every 28-day cycle and cycle 1, day 15). Patients were stratified by presence of liver/lung metastases and prior ET. The primary end point was mean duration of PFS as assessed by investigators. Secondary end points included safety and time to definitive 10% deterioration from baseline (TTD) and change from baseline in global health status/quality of life (GHS/QoL) scale scores (measured by European Organisation for Research and Treatment of Cancer Quality of Life Core 30 Questionnaire). Pain scores were determined using the Brief Pain Inventory, Short Form.
Results: The study included 726 patients and had a median duration of 20.4 months from randomization to data cutoff. Median PFS for ribociclib (n = 484) vs placebo (n = 242) was 20.5 months (95% CI, 18.5-23.5) vs 12.8 months (95% CI, 10.9-16.3), respectively (hazard ratio [HR] 0.593; 95% CI, 0.480-0.732; P = .00000041). The PFS benefit associated with ribociclib was consistent between ET-naive patients (n = 367; HR 0.577; 95% CI, 0.415-0.802) and ET-exposed patients (n = 345; HR 0.565; 95% CI, 0.428-0.744). Most common adverse events for ribociclib vs placebo were neutropenia (70% vs 2%), nausea (45% vs 28%), and fatigue (31% vs 33%), respectively. For the ribociclib group, grades 3 and 4 neutropenia (47%, 7%),3 increased alanine aminotransferase (7%, 2%), and increased aspartate aminotransferase (5%, 1%) were reported.5 Postbaseline QT interval corrected by Fridericia’s formula >480 msec was also reported in the ribociclib (6%) and placebo (3%) groups. Mean GHS/QoL was maintained or improved from baseline during every cycle of treatment in both groups up to cycle 19 (mean change from baseline, ribociclib, 3.6-4.9; placebo, 1.3-4.3). At the end of treatment, ribociclib did not negatively affect the mean change from baseline GHS/QoL (ribociclib, n = 184, –5.2 points; placebo, n = 113, –5.5 points). Median TTD for GHS/QoL for ribociclib vs placebo, respectively, was not reached (NR) vs 19.4 months (HR 0.80; 95% CI, 0.60-1.05); for worst pain, 25.4 months vs NR (HR 0.81; 95% CI, 0.58-1.13); and for pain severity, 25.4 months vs NR (HR 0.81; 95% CI, 0.60-1.11). Median TTD for pain interference index was NR in both groups.
Conclusions: The addition of ribociclib with fulvestrant significantly prolonged PFS, demonstrated a manageable safety profile, and maintained QoL in postmenopausal patients with HR+/HER2− ABC who had previously received ≤1 line of ET for advanced disease.
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