Ribociclib Benefit After Breast Cancer Surgery Persists at Year 5: The NATALEE Trial
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3 Years of Treatment, 5 Years of Benefit
ESMO 2025findings from the NATALEE trialshowed that patients with early-stage HR-positive / HER2-negative breast cancer who received postsurgical ribociclib (400 mg, 3 years) + NSAI (nonsteroidal aromatase inhibitor) treatment maintained a disease-free survival advantage even at 5 years of follow-up .
In the large patient population of the trial, invasive disease-free survival (iDFS) was 85.5% in the ribociclib arm and 81.0% in the NSAI-alone arm (HR 0.716, 95% CI 0.618–0.829). This corresponds to approximately a 30% reduction in recurrence risk and a 4.5% absolute difference. In addition, for overall survival (OS), a favorable trend for ribociclib was observed (HR 0.80).
The findings support the potential for lymph node-positive (N+) and high-risk early-stage patients to receive, through prolonged adjuvant CDK4/6 inhibition strategies, lasting protection . ESMO 2025 thus became a milestone reinforcing the paradigm of ‘3 years of treatment, 5 years of benefit’ for adjuvant ribociclib use.
Summary: At 5 years of follow-up, ribociclib + NSAIprovides, compared with NSAI alone, a sustained advantage in iDFS and DDFS . The favorable OS trend is strengthening, but remains immature. There are no new safety signals.
5-Year iDFS – Comparative View (Horizontal)
Absolute difference: +4.5% | HR: 0.716 (95% CI 0.618–0.829)
Study Design
| Item | Information |
|---|---|
| Population | Stage II–III HR+/HER2− early breast cancer (n≈5101); includes N0 (with additional risk factors) and N+ |
| Intervention | Ribociclib 400 mg (21/28 days) 36 months + NSAI 60 months vs NSAI alone for 60 months; goserelin in premenopausal patients |
| Primary Endpoint | iDFS (invasive disease-free survival) |
| Secondary | DDFS, DRFS, OS, safety |
| Follow-up | Median iDFS follow-up ≈55.4 months; all patients had stopped RIB; NSAI completion rates were similar between arms |
Main Results
- iDFS (5 years): 85.5% vs 81.0% (absolute +4.5%); HR 0.716 (95% CI 0.618–0.829; nominal 1-sided p<.0001).
- DDFS: HR 0.709 (95% CI 0.608–0.827); DRFS: HR 0.699 (95% CI 0.594–0.824).
- OS: Favorable trend (HR 0.800, 95% CI 0.637–1.003; nominal p=0.026) — data are immature.
- Subgroups: Benefit was broadly consistent. In N0 patients, the confidence interval may cross 1.0 at interim analyses → careful patient selection.
- Safety: No new signals with extended follow-up; the tolerability advantage of the 400 mg dose persists.
DROZDOGAN Academy Commentary
Adjuvant use of CDK4/6 inhibitors requires studies planned specifically for our country that focus on cost and quality of life . Although long-term follow-up has shown a statistically significant survival difference , translating this difference into daily clinical practice is often difficult.
Given the nature of treatment, patients remain under close monitoring for 2–3 years ; this process requires numerous outpatient visits, blood tests and cardiac assessments . The survival gain must therefore be evaluated holistically alongside the burden of toxicity, monitoring costs and healthcare resource use .
Conducting analyses that take account of our country’s socioeconomic conditions and potential racial/genetic differences is essential. These pharmacoeconomic and patient-centered analyses are essential. This would allow the adjuvant use of CDK4/6 inhibitors to have its real-world valueassessed in terms of clinical efficacy, quality of life and cost, and objectively established.
Impact on Practice – Quick Guide
- Standard ET + Ribociclib (400 mg, 3 years) is a strong approach for Stage II–III and/or N+ patients.
- For N0 patients at borderline risk : The absolute gain may be limited → treatment should be determined through shared decision-making and the individual risk profile.
- Follow-up: Closely monitor OS data and long-term toxicity through post-ESMO updates.
3 Frequently Asked Questions
- Is there an OS benefit? For now there is a trend ; statistical maturity is awaited.
- Why 400 mg? To improve tolerability during prolonged use and maximize treatment persistence.
- What should we do for an N0 patient? The absolute benefit may be small; be sure to weigh age, comorbidities, risk factors and patient preference.
Source: Crown JP, et al. Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC): NATALEE 5-year outcomes. ESMO Congress 2025 – LBA14.
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