MONALEESA-3
Trial question
What is the effect of ribociclib plus fulvestrant in patients with HR+/HER2- advanced breast cancer?
Study design
Multi-center
Double blinded
RCT
Population
726 female patients.
Inclusion criteria: adult patients with HR+/HER2- advanced breast cancer.
Key exclusion criteria: symptomatic visceral disease or disease burden rendering patients ineligible for endocrine therapy; prior treatment with chemotherapy, fulvestrant, or any CDK4/6 inhibitors; inflammatory breast cancer; CNS involvement; clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
Interventions
N=484 ribociclib plus fulvestrant (ribociclib 600 mg PO daily for 21 consecutive days, followed by 7 days off, for a complete cycle of 28 days plus fulvestrant 500 mg IM on day 1 of each 28-day cycle with an additional dose on day 15 of cycle 1).
N=242 placebo plus fulvestrant (matching placebo for 21 consecutive days, followed by 7 days off, for a complete cycle of 28 days plus fulvestrant 500 mg IM on day 1 of each 28-day cycle with an additional dose on day 15 of cycle 1).
Primary outcome
Overall survival at 42 months
57.8%
45.9%
57.8 %
43.3 %
28.9 %
14.4 %
0.0 %
Ribociclib plus
fulvestrant
Placebo plus
fulvestrant
Significant
increase ▲
NNT = 8
Significant increase in overall survival at 42 months (57.8% vs. 45.9%; HR 1.39, 95% CI 1.09 to 1.75).
Secondary outcomes
Significant increase in median progression-free survival in patients receiving first-line therapy (33.6 months vs. 19.2 months; HR 1.82, 95% CI 1.39 to 2.38).
Significant increase in median progression-free survival in the overall population (20.6 months vs. 12.8 months; HR 1.69, 95% CI 1.41 to 2.04).
Significantly longer time to first chemotherapy at 42 months (56.4% vs. 43.7%; HR 1.43, 95% CI 1.14 to 1.82).
Safety outcomes
No significant difference in prolonged QT interval.
Significant difference in grade 3 or 4 neutropenia (57.1% vs. 0.8%) and leukopenia (15.5% vs. 0%).
Conclusion
In adult patients with HR+/HER2- advanced breast cancer, ribociclib plus fulvestrant was superior to placebo plus fulvestrant with respect to overall survival at 42 months.
Reference
Dennis J Slamon, Patrick Neven, Stephen Chia et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020 Feb 6;382(6):514-524.
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