Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in NATALEE: Analysis across menopausal status and age.

516 Background: The NATALEE trial demonstrated significant invasive disease–free survival benefit with RIB + NSAI vs NSAI alone in patients (pts) with stage II/III HR+/HER2− early breast cancer (EBC) at high risk of recurrence. Here, we report outcomes by menopausal status and age. Methods: Pts were treated with RIB + NSAI or NSAI alone in NATALEE; premenopausal (PreM) women also received goserelin. Men were excluded from this analysis. Efficacy, safety, and quality of life were analyzed by menopausal status (assessed at randomization or start of adjuvant endocrine therapy, whichever was first) and age (PreM [<40 y, ≥40 y]; postmenopausal [PostM; <60 y, ≥60 y]). Data cutoff was April 29, 2024. Results: A greater portion of PreM vs PostM pts had ECOG performance status 0 (86.8% vs 80.1%), Ki-67 >20% (39.9% vs 34.4%), N1-N3 nodal stage (63.4% vs 56.9%), and T3/T4 tumors (28.7% vs 24.0%) at diagnosis. There was consistent treatment benefit with RIB + NSAI vs NSAI alone across groups and ages (median follow-up, 44.2 months) (Table). Fewer PreM pts discontinued RIB due to AEs vs PostM (16.1% vs 22.9%); reductions due to AEs were similar (22.4% vs 23.6%). Of pts who discontinued due to AEs, more PreM pts did so without a dose reduction vs PostM (75.4% vs 67.5%). Within menopausal groups, fewer pts in the younger cohorts discontinued RIB due to AEs (Table). Alanine aminotransferase elevation was the most common AE leading to discontinuation in the PreM (6.2%) and PostM groups (8.0%). Time to deterioration in global and physical functioning scales of the EORTC QLQ-C30 was similar between treatment arms for all subgroups. Conclusions: RIB + NSAIprovides treatment benefit to a broad range of pts with stage II/III HR+/HER2− EBC across menopausal status and age. In younger PreM pts, who typically have more aggressive disease characteristics, treatment favored RIB + NSAI, and these pts were least likely to discontinue RIB due to AEs. Clinical trial information: NCT03701334 . PreM (n = 2238) PostM (n = 2844) Hazard ratio a (95% CI) All RIB = 1115 NSAI = 1123 <40 y RIB = 237 NSAI = 276 ≥40 y RIB = 878 NSAI = 847 All RIB = 1424 NSAI = 1420 <60 y RIB = 703 NSAI = 735 ≥60 y RIB = 721 NSAI = 685 Invasive disease–free survival 0.671(0.518-0.870) 0.690(0.419-1.137) 0.662(0.488-0.897) 0.746(0.607-0.917) 0.835(0.619-1.128) 0.673(0.506-0.896) Distant disease–free survival 0.655(0.498-0.861) 0.647(0.383-1.091) 0.659(0.478-0.908) 0.759(0.612-0.941) 0.854(0.625-1.168) 0.681(0.506-0.916) Recurrence–free survival 0.641(0.486-0.845) 0.723(0.429-1.220) 0.610(0.439-0.846) 0.735(0.588-0.919) 0.811(0.590-1.114) 0.668(0.487-0.915) Disposition in RIB arm, n (%) RIB discontinuation due to AE 179 (16.1) 25 (10.5) 154 (17.5) 326 (22.9) 125 (17.8) 201 (27.9) RIB reduction due to AE 248 (22.4) 64 (27.0) 184 (21.1) 332 (23.6) 169 (24.2) 163 (22.9) a Hazard ratios between treatment arms (RIB + NSAI; NSAI alone), stratified by stage, prior chemotherapy, and geographic region.