Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival
John Crown, Daniil Stroyakovskii, Denise A. Yardley, Chiun‐Sheng Huang, Peter A. Fasching, Amit Bardia, S. Chia, Seock‐Ah Im, Miguel Martín, B. Xu, Carlos H. Barrios, Michael Untch, R Moroose, Sara A. Hurvitz, Gabriel N. Hortobágyi, Dennis J. Slamon, F. Visco, Gonzalo Spera, Juan Pablo Zarate, Doug N. Halligan, Zheng Li, Sherene Loi
Abstract
At the primary efficacy analysis of the NATALEE phase III trial, ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) demonstrated a statistically significant improvement in invasive disease-free survival (iDFS) versus NSAI alone in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC). Continued follow-up of efficacy outcomes is important in assessing the durability of treatment benefit. We report 5-year estimates of efficacy outcomes, including an udpated analysis of overall survival (OS). Eligible patients included pre/postmenopausal women and men with HR-positive/HER2-negative EBC and anatomic stage IIA (N1 or N0 with high-risk factors), IIB, or III disease. Patients were randomized 1 : 1 to ribociclib 400 mg/day (3 weeks on/1 week off for 3 years) + NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 5 years) or NSAI alone. Premenopausal women and men received goserelin. The primary endpoint was iDFS, and secondary/exploratory endpoints included distant disease-free survival, recurrence-free survival, distant recurrence-free survival, and OS. With a median iDFS follow-up of 55.4 months, ribociclib + NSAI demonstrated persistent iDFS benefit versus NSAI alone [hazard ratio 0.716, 95% confidence interval (CI) 0.618-0.829, nominal one-sided log-rank P < 0.0001]. Absolute iDFS improvement between treatment arms increased from the 3- (Δ2.7%) to the 5-year (Δ4.5%) time points. Persistent benefit over time was also observed across subgroups [including N0 patients (hazard ratio 0.606, 95% CI 0.372-0.986)] and secondary/exploratory endpoints. As OS continues to mature, numerical improvement in favor of ribociclib was observed (hazard ratio 0.800, 95% CI 0.637-1.003, nominal one-sided log-rank P = 0.026). This prespecified 5-year follow-up of efficacy outcomes from NATALEE demonstrated that ribociclib + NSAI continued to reduce the risk of recurrence beyond the 3-year treatment window, supporting its use as adjuvant therapy in patients with HR-positive/HER2-negative EBC. An ongoing positive trend for improved OS in favor of ribociclib + NSAI was observed. • This prespecified analysis assessed 5-year efficacy outcomes of the NATALEE trial (median iDFS follow-up of 55.4 months). • Persistent iDFS benefit was observed with ribociclib + NSAI versus NSAI alone (hazard ratio 0.716, 95% CI 0.618-0.829). • iDFS benefit with ribociclib was observed across subgroups, including in node-0 disease (hazard ratio 0.606, 95% CI 0.372-0.986). • A positive trend for OS in favor of ribociclib continues to emerge (hazard ratio 0.800, 95% CI 0.637-1.003, nominal one-sided P = 0.026). • No new safety signals for causes of deaths or secondary primary malignancies were identified with this updated analysis.