Baseline (BL) characteristics and efficacy endpoints for patients (pts) with node-negative (N0) HR+/HER2− early breast cancer (EBC): NATALEE trial.
Authors: Yardley Denise A. , Untch Michael , Barrios Carlos H. , Bardia Aditya , Kalinsky Kevin , Im Seock-Ah , Chia Stephen K. L. , Ring Alistair E. , McAndrew Nicholas Patrick , Valero Vicente , Ruiz-Borrego Manuel , Fresco Rodrigo , Sum Eleanor , Chattar Yogesh , Waters Sorcha , Harbeck Nadia 
Published: May 2024

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Background: NATALEE assessed ribociclib (RIB) + non-steroidal aromatase inhibitor (NSAI) vs NSAI alone in pts with HR+/HER2− EBC at increased risk of recurrence, including pts with N0 disease, and showed a statistically significant invasive disease-free survival (iDFS) benefit. We report BL characteristics, efficacy, and safety for the N0 subgroup. Methods: Pts with stage II/III HR+/HER2− EBC were randomized (R) 1:1 to RIB 400 mg/d (3 wk on/1 wk off for 36 mo) + NSAI (letrozole or anastrozole for ≥60 mo) or NSAI alone. Men and premenopausal women received goserelin. Pts could receive any standard (neo)adjuvant endocrine therapy (ET) ≤12 mo before randomization. In the intent-to-treat (ITT) population, 78% of pts completed 3y of RIB treatment (tx) or discontinued early with 21% still on tx at the time of this analysis (data cutoff: July 21, 2023; median follow up, 33 mo). The N0 subgroup included pts with T2N0 (stage IIA; with grade [G]3, or G2 disease and Ki-67 ≥20% or high genomic risk [HGR]), T3N0 (stage IIB), and T4N0 (stage IIIB); T1N0 was excluded. Results: Of 2549 pts R to RIB + NSAI and 2552 to NSAI alone, 285 (11%) and 328 (13%) had N0 disease, respectively. BL characteristics for the N0 subgroup were balanced across arms. Most pts were premenopausal (RIB + NSAI: 67% vs NSAI alone: 63%). Pts with N0 disease had anatomic stage IIA (RIB + NSAI: 74% vs NSAI alone: 73%), stage IIB (17% vs 13%), or stage IIIB (9% vs 12%) disease (Table). Most pts received prior chemotherapy (RIB + NSAI: 72% vs NSAI alone: 71%); prior ET was received by 59% vs 62% of pts with RIB + NSAI vs NSAI alone. For pts with T2N0 disease treated with RIB + NSAI vs NSAI alone, 49% vs 45% had G3 disease and 49% vs 53% had G2 disease (54% vs 56% with T2N0, G2 & Ki-67 > 20%; 13% vs 23% with T2N0, G2, Ki-67 ≤20%/missing & HGR). Consistent with the ITT population, RIB + NSAI improved iDFS (HR, 0.72; 95% CI, 0.41-1.27; 3y rate with RIB + NSAI vs NSAI alone, 93.2% vs 90.6%), distant disease–free survival (DDFS; HR, 0.70; 95% CI, 0.38-1.29; 3y rate, 94.3% vs 91.5%), and distant recurrence–free survival (DRFS; HR, 0.58; 95% CI, 0.29-1.17; 3y rate, 96.3% vs 92.5%) in pts with high-risk N0 disease. The safety profile of RIB in the N0 subgroup was consistent with the ITT population. The rate of discontinuation due to all grade adverse events was 24% vs 8% with RIB + NSAI vs NSAI alone. Conclusions: This analysis showed a consistent efficacy benefit and manageable safety profile of RIB + NSAI vs NSAI alone in pts with N0 disease in NATALEE. The 3y iDFS, DDFS, and DRFS rates in the control arm at this early follow-up underscore the risk of recurrence for the N0 subgroup. These findings support the use of RIB in pts with HR+/HER2− EBC at increased risk of recurrence, including pts with N0 disease. Clinical trial information: NCT03701334 . [Table: see text]