Kefah Mokbel, Professor of Medicine at Cardiff University School of Medicine, shared on LinkedIn:
“A major milestone for adjuvant ribociclib in early breast cancer: overall survival benefit at 6 years!
Exciting results presented today at ESMO2026 from the phase III NATALEE trial, providing further evidence for the long-term benefit of ribociclib plus endocrine therapy in patients with HR+/HER2− early breast cancer.
For the first time, NATALEE reports a positive overall survival (OS) benefit, alongside sustained improvements in invasive disease-free survival (iDFS).
Key findings at 6 years:
- Overall survival: HR 0.809 (95% CI: 0.661–0.989), corresponding to a 19.1% relative reduction in the hazard of death.
- 6-year OS: 91.86% vs 89.73% — an absolute improvement of 2.1%.
- Invasive disease-free survival: HR 0.741 (95% CI: 0.646–0.849), with an absolute benefit of 5.3% at 6 years (83.23% vs 77.92%).
- Benefits in distant disease-free survival and distant recurrence-free survival were also maintained.
- No new safety signals were identified.
What makes these results particularly compelling?
Patients had been off ribociclib for a median of approximately 38 months, yet the benefits continued to persist and deepen over time.
This is an important development in the adjuvant treatment landscape, where preventing recurrence is critical, but demonstrating an overall survival benefit remains the ultimate goal.
These findings further strengthen the evidence supporting ribociclib plus endocrine therapy for eligible patients with stage II/III HR+/HER2− early breast cancer.
The findings translate to approximately 19 patients treated to prevent one additional iDFS event by 6 years (1 ÷ 0.053), although iDFS includes events other than distant breast cancer recurrence. The 2.1% absolute OS benefit is encouraging, but it is smaller and needs interpretation alongside treatment toxicity, cost, and patient selection.
The question now: Can CDK4/6 inhibition plus optimal endocrine therapy replace chemotherapy in selected patients with high genomic risk?”
You can also read: NATALEE: Ribociclib Delivers Overall Survival Benefit at 6 Years in HR+/HER2− Early Breast Cancer.
