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Ribociclib Plus Endocrine Therapy in Hormone Receptor-Positive/ERBB2-Negative Early Breast Cancer: 4-Year Outcomes
Peter A Fasching1, Daniil Stroyakovskiy2, Denise A Yardley3
1University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Importance:
Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) has demonstrated a statistically significant invasive disease-free survival (iDFS) benefit over NSAI alone in patients with hormone receptor-positive/ERBB2 (formerly HER2)-negative early breast cancer. Evaluating the efficacy and safety of adjuvant ribociclib beyond the planned 3-year treatment period is critical for understanding the long-term impact on recurrences.
Objective:
To evaluate efficacy and safety of adjuvant ribociclib in an exploratory 4-year analysis of the NATALEE (New Adjuvant Trial With Ribociclib [LEE011]) randomized clinical trial, with all patients no longer receiving ribociclib treatment.
Design, Setting, And Participants:
This exploratory analysis of an international, open-label, randomized phase 3 trial analyzed adjuvant treatment for premenopausal and postmenopausal women and men with hormone receptor-positive/ERBB2-negative early breast cancer. Eligible patients had anatomic stage IIA (either N0 with additional risk factors or N1 [1-3 axillary lymph nodes]), IIB, or III disease per the American Joint Committee on Cancer Staging Manual, eighth edition. The data cutoff date was April 29, 2024.
Interventions:
Patients were randomized 1:1 to receive ribociclib (400 mg once daily, days 1-21 of a 28-day cycle, over 36 months) plus NSAI (letrozole, 2.5 mg, or anastrozole, 1 mg, once daily continuously for 60 months) or NSAI alone. Men and premenopausal women also received goserelin (3.6 mg once every 28 days administered subcutaneously).
Main Outcomes And Measures:
The primary end point was iDFS, and secondary efficacy end points included distant disease-free survival, recurrence-free survival, and overall survival. Survival was evaluated by the Kaplan-Meier method.
Results:
Among 5101 patients included in the analysis (median [range] age, 52 [24-90] years; 5081 [99.6%] female), the median follow-up for iDFS was 44.2 months (range, 0-63 months). Ribociclib plus NSAI continued to show iDFS benefit over NSAI alone (hazard ratio, 0.72; 95% CI, 0.61-0.84), with 3-year iDFS rates of 90.8% vs 88.1% (difference, 2.7 percentage points) and 4-year rates of 88.5% vs 83.6% (difference, 4.9 percentage points). The efficacy benefit was consistent across subgroups and secondary end points. Overall survival data remain immature, although a trend in favor of ribociclib plus NSAI over NSAI alone was observed (hazard ratio, 0.83; 95% CI, 0.64-1.07). The incidence of adverse events has remained stable.
Conclusions And Relevance:
This exploratory analysis of the NATALEE randomized clinical trial, with a median follow-up beyond the 3-year treatment duration, demonstrated consistent iDFS benefit with ribociclib plus NSAI over NSAI alone.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03701334.
Insights
Adjuvant ribociclib combined with a nonsteroidal aromatase inhibitor (NSAI) significantly improved invasive disease-free survival (iDFS) in early breast cancer patients. This benefit persisted beyond the planned 3-year treatment, showing sustained efficacy in longer-term follow-up.
Area of Science:
- Oncology
- Clinical Trials
- Pharmacology
Background:
- Hormone receptor-positive/ERBB2-negative early breast cancer remains a significant health concern.
- Adjuvant therapy aims to reduce recurrence risk after primary treatment.
- Ribociclib (LEE011) plus a nonsteroidal aromatase inhibitor (NSAI) showed a disease-free survival benefit in the NATALEE trial.
Purpose of the Study:
- To evaluate the long-term efficacy and safety of adjuvant ribociclib plus NSAI versus NSAI alone.
- To assess invasive disease-free survival (iDFS) beyond the planned 3-year treatment period.
- To analyze the sustained impact of ribociclib on recurrence rates in early breast cancer.
Main Methods:
- Exploratory analysis of the international, open-label, randomized phase 3 NATALEE trial.
- Patients received either ribociclib (36 months) plus NSAI (60 months) or NSAI alone.
- Primary endpoint: iDFS. Secondary endpoints: distant disease-free survival, recurrence-free survival, overall survival. Kaplan-Meier method used for survival evaluation.
Main Results:
- Median follow-up of 44.2 months in 5101 patients.
- Ribociclib plus NSAI demonstrated a continued iDFS benefit (HR, 0.72).
- 4-year iDFS rates were 88.5% for ribociclib + NSAI vs. 83.6% for NSAI alone, showing a 4.9 percentage point difference.
Conclusions:
- Adjuvant ribociclib plus NSAI provides a consistent and sustained iDFS benefit in hormone receptor-positive/ERBB2-negative early breast cancer.
- The efficacy observed extends beyond the 3-year treatment duration.
- These findings support the long-term value of combining ribociclib with NSAI for adjuvant therapy in this patient population.
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