D. Slamon, P. Neven, S. Chia
May 15, 2021
Citations
5
Influential Citations
128
Citations
Quality indicators
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
Abstract
BACKGROUND Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase 3 CDK4/6 inhibitor clinical trial in patients with ABC (median [m], 56.3 months). PATIENTS AND METHODS This phase 3, randomized, double-blind, placebo-controlled trial was conducted at 174 sites (30 countries). Patients were me and postmenopausal women (age ≥18 years) with histologically/cytologically confirmed HR+/HER2- ABC. Patients could have received ≤1-line endocrine therapy (ET) but no chemotherapy for ABC. Patients, assigned 2:1, were stratified by presence/absence of liver/lung metastases and previous ET. Patients received intramuscular fulvestrant (500 mg, day 1 each 28-day cycle, plus day 15 of cycle 1) with oral ribociclib (600 mg/day; 3-weeks-on,1-week-off) or placebo. Efficacy analyses were by intention-to-treat. Safety was assessed in patients receiving ≥1 dose study treatment. OS was a secondary endpoint. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615; no longer enrolling). RESULTS Between June 18, 2015 and June 10, 2016, 726 patients were randomly assigned (484, ribociclib; 242, placebo). At data cutoff (October 30, 2020), mOS was 53.7 months (ribociclib) versus 41.5 months (placebo) (hazard ratio [HR], 0.73; 95% CI, 0.59-0.90). Subgroup analyses were consistent with overall population. In the first-line setting, most patients in the ribociclib arm (≈60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI, 0.46-0.88). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI, 0.59-1.04). No apparent drug-drug interaction between ribociclib and fulvestrant or new safety signals were observed. CONCLUSIONS This analysis reported extended OS follow-up in MONALEESA-3. mOS was ≈12 months longer in patients with HR+/HER2- ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy.