Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in NATALEE: Analysis across menopausal status and age.
Abstract
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (17)
Kevin Kalinsky
Winship Cancer Institute, Emory University, Atlanta
Mattea Reinisch
Breast Unit, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany
Yen-Shen Lu
Department of Medical Oncology, National Taiwan University Hospital, Cancer Center Branch
Marc Debled
Institut Bergonié, Bordeaux, France
Binghe Xu
Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
Lowell Hart
Florida Cancer Specialists, Sarah Cannon Research Institute and Wake Forest University School of Medicine, Fort Myers and Winston-Salem, NC, FL
Stephanie L. Graff
Brown University Health Cancer Institute, The Warren Alpert Medical School of Brown University, Providence, RI
Qiang Liu
Michael Untch
From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine–UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) — both in Pittsburgh; AGO-B and Helios Klinikum Berlin–Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie–Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen–EMN, Friedrich–Alexander University Erlangen–Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) — all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine,...
Sherene Loi
Priyanka Sharma
Viktoriya Sakalosh
Translational Research in Oncology (TRIO), Tuscany, Italy
Melissa Gao
Novartis Pharma AG, Basel, Switzerland
Elizabeth Chertow Santarsiero
Novartis Pharmaceuticals Corporation, East Hanover, NJ
Sorcha Waters
Novartis Ireland, Dublin, Ireland
Shaheen Islam
Medical College of Georgia, McDonough, Georgia, United States
Seock-Ah Im
Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea