21 Ribociclib (RIB) + Nonsteroidal Aromatase Inhibitor (NSAI) as Adjuvant Treatment in Patients (pts) With HR+/HER2– Early Breast Cancer (EBC): Final Invasive Disease-Free Survival (iDFS) Analysis From the NATALEE Trial

21 Ribociclib (RIB) + Nonsteroidal Aromatase Inhibitor (NSAI) as Adjuvant Treatment in Patients (pts) With HR+/HER2– Early Breast Cancer (EBC): Final Invasive Disease-Free Survival (iDFS) Analysis From the NATALEE Trial

Background

Interim results from the phase 3 NATALEE trial showed that ribociclib added to standard-of-care adjuvant nonsteroidal aromatase inhibitor (NSAI) had a significant invasive disease-free survival (iDFS) benefit in patients with stage II/III HR+/HER2- early breast cancer (EBC) at risk of recurrence, including those with node-negative disease. We present the final protocol-specified analysis of iDFS (primary end point).

Previously presented at 2023 San Antonio Breast Cancer Symposium, final publication number: GS03-03, Gabriel Hortobagyi, et al. Reused with permission.

Methods

A total of 5101 pre-/postmenopausal women and men were randomly assigned (1:1 ratio) to ribociclib (400 mg/day; 3 weeks on/1 week off for 36 months) plus NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 60 months or more) or NSAI alone. Men and premenopausal women received goserelin (3.6mg once every 28 days). Eligible patients had stage IIA/B or III BC per American Joint Committee on Cancer, eighth edition. Patients stayed on trial if they continued on NSAI (5 years or less) regardless of ribociclib discontinuation. Primary end point: iDFS per STEEP v1.0 criteria. Secondary efficacy end points: recurrence-free survival (RFS), distant (DDFS), and overall survival (OS).

Results

At data cutoff (July 21, 2023), among the 2549 patients in the ribociclib plus NSAI arm, 1091 (42.8%) completed 3 years of ribociclib and 905 (35.5%) discontinued ribociclib or ribociclib plus NSAI early. Additionally, 528 patients (20.7%) stayed on ribociclib. Of note, 1748 patients (68.5%) remain on treatment in the NSAI arm. The median follow-up for iDFS was 33.3 months, an extra 5.6 months from the previous interim analysis. There were 509 iDFS events (226 [8.9%] with RIB + NSAI and 283 [11.1%] with NSAI alone). Ribociclib plus NSAI showed a significant iDFS benefit vs NSAI alone (HR, 0.749; 95% CI, 0.628-0.892;
P = .0006). The 3-year iDFS rates were 90.7% (95% CI, 89.3%-91.8%) vs 87.6% (95% CI, 86.1%-88.9%). A consistent benefit was seen across patient subgroups including those with node-negative, stage II, or stage III disease. Secondary end points of DDFS and RFS favored ribociclib plus NSAI vs NSAI alone. The OS data were immature (total events: 84 [3.3%] with ribociclib plus NSAI and 88 [3.4%] with NSAI alone). No new safety signals were observed. Discontinuation of RIB due to adverse events was observed in 19.5% of patients.

Conclusions

With a substantial proportion of patients completing 3 years of ribociclib treatment, NATALEE continues to show a significant iDFS improvement with ribociclib plus NSAI vs NSAI alone. Efficacy results confirm continued improvement in benefit across subgroups. Safety findings support the manageable toxicity profile of RIB at the 400-mg starting dose in EBC.