As reported in The New England Journal of Medicine by Dennis Slamon, MD, PhD, and colleagues, interim analysis of the phase III NATALEE trial has shown improved invasive disease–free survival with the addition of adjuvant ribociclib to a nonsteroidal aromatase inhibitor (NSAI) in patients with hormone receptor–positive, HER2-negative early breast cancer.

Dennis Slamon, MD, PhD

Study Details

In the international open-label trial, 5,101 patients with stage II or III disease were randomly assigned between January 2019 and April 2021 to re­ceive adjuvant ribociclib at 400 mg per day for 3 weeks followed by 1 week off for 3 years plus an NSAI (n = 2,549) or an NSAI alone (n = 2,552). NSAI treatment consisted of letrozole at 2.5 mg per day or anastrozole at 1 mg per day for ≥ 5 years. Premenopausal women and men also received goserelin every 28 days. Approximately 60% of patients in each group had stage III disease; approximately 71% had received prior endocrine therapy; and 43% and 48% had received prior neoadjuvant and prior adjuvant chemotherapy, respectively. The primary endpoint of the interim analysis was invasive disease–free survival.

Invasive Disease–Free Survival

At time of the prespecified interim analysis, median follow-up was 34 months. At 3 years, invasive disease–free survival was 90.4% with ribociclib plus an NSAI vs 87.1% with an NSAI alone (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.62–0.91, P = .003). At 3 years, the absolute invasive disease–free survival benefit with ribociclib plus an NSAI was 3.0 percentage points among patients with stage II disease and 3.2 percentage points among those with stage III disease.

At 3 years, distant disease–free survival was 90.8% vs 88.6% (HR = 0.74, 95% CI = 0.60–0.91) and recurrence-free survival was 91.7% vs 88.6% (HR = 0.72, 95% CI = 0.58–0.88). At time of analysis, death had occurred in 2.4% of patients in the ribociclib plus NSAI group vs 2.9% of the NSAI alone group (HR = 0.76, 95% CI = 0.54–1.07).

Adverse Events

Grade 3, 4, and 5 adverse events occurred in 56.9%, 5.2%, and 0.5% of patients in the ribociclib plus NSAI group, respectively, and 16.1%, 1.6%, and 0.2% of the NSAI group. The most common grade 3 or 4 adverse event in the ribociclib plus NSAI group was neutropenia (48.1% grade 3 and 2.1% grade 4, compared with 0.7% and 0.1% in the NSAI alone group). Serious adverse events occurred in 13.3% vs 9.9% of patients. Adverse events led to discontinuation of ribociclib in 18.9% of patients. No deaths were considered related to treatment.

The investigators concluded, “Ribociclib plus an NSAI significantly improved invasive disease–free survival among patients with [hormone receptor–]positive, HER2-negative stage II or III early breast cancer.”

Dr. Slamon, of the Da­vid Geffen School of Medicine at the Uni­versity of California, Los Angeles, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The study was funded by Novartis. For full disclosures of the study authors, visit nejm.org.