Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2− early breast cancer: primary results from the phase III NATALEE trial (#248)

Dennis Slamon 1 , Daniil Stroyakovskiy 2 , Denise A. Yardley 3 , Chiun-Sheng Huang 4 , Peter A. Fasching 5 , John Crown 6 , Aditya Bardia 7 , Stephen Chia 8 , Seock-Ah Im 9 , Miguel Martin 10 , Sherene Loi 11 , Binghe Xu 12 , Sara Hurvitz 13 , Carlos Barrios 14 , Michael Untch 15 , Belinda Yeo 16 , Rebecca Moroose 17 , Frances Visco 18 , Rodrigo Fresco 19 , Tetiana Taran 20 , Gabriel N. Hortobagyi 21
  1. David Geffen School of Medicine at UCLA, CA, USA
  2. Moscow City Oncology Hospital #62 of Moscow Healthcare Department, Moscow Oblast, Russia
  3. Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA
  4. National Taiwan University Hospital, National Taiwan University College of Medicine , Taipei City, Taiwan
  5. University Hospital Erlangen Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, , Erlangen, Germany
  6. St. Vincents Hospital, Dublin, Ireland
  7. Mass General Cancer Center, Harvard Medical School, Boston, MA, USA
  8. British Columbia Cancer Agency, , Vancouver, BC, Canada
  9. Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
  10. Instituto de Investigación Sanitaria Gregorio Marañon, Centro de Investigación Biomédica en Red de Cáncer, Grupo Español de Investigación en Cáncer de Mama, Universidad Complutense , Madrid, Spain
  11. Peter MacCallum Cancer Centre, Melbourne, , Australia
  12. Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), and Peking Union Medical College (PUMC), Beijing, China
  13. University of California, Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
  14. Latin American Cooperative Oncology Group (LACOG),, Porto Alegre, Brazil
  15. Interdisciplinary Breast Cancer Center, , Helios Klinikum Berlin-Buch, Germany
  16. Olivia Newton-John Cancer Research Institute, Austin Hospital, Heidelberg, Melbourne, VIC, Australia
  17. Orlando Health Cancer Institute, Orlando, FL, USA
  18. National Breast Cancer Coalition (NBCC), Washington DC, USA
  19. TRIO - Translational Research in Oncology, Montevideo, Uruguay
  20. Novartis Pharma AG, Basel, Switzerland
  21. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Background

The phase III NATALEE trial (NCT03701334) evaluated adjuvant ribociclib+endocrine therapy (ET) in a broad population of patients with stage II/III HR+/HER2− early breast cancer (EBC) at risk for recurrence, including patients with no nodal involvement (N0).

Methods  

Men and pre- or postmenopausal women were randomized 1:1 to ribociclib (400 mg/day; 3 week on/1 week off for 3 years) + ET (letrozole 2.5 mg/day or anastrozole 1 mg/day, for ≥5 years) or ET alone. Men and premenopausal women also received goserelin. Eligible patients had ECOG PS­ 0-1 and stage IIA (either N0 with additional risk factors or 1-3 axillary lymph nodes), stage IIB, or stage III EBC per AJCC; prior (neo)adjuvant ET was allowed if initiated ≤12 month before randomization. This prespecified interim analysis of invasive disease-free survival (iDFS, primary-endpoint), defined per STEEP criteria, was planned after ≈425 events (≈85% of planned total).

Results

5101 patients were randomized (ribociclib+ET, n=2549; ET alone, n=2552). As of the data cutoff (11 Jan 2023), median follow-up was 34 months (min, 21 months). 3- and 2-year ribociclib treatment was completed by 515 patients (20.2%) and 1449 patients (56.8%), respectively; 3810(74.7%) remained on study treatment (ribociclib+ET, n=1984; ET alone, n=1826). iDFS was evaluated after 426 events (RIB+ET, n=189; ET alone, n=237). Ribociclib+ET demonstrated significantly longer iDFS than ET alone (HR, 0.748; 95%CI, 0.618-0.906; P=.0014); 3-year iDFS rates were 90.4% vs 87.1%. iDFS benefit was generally consistent across stratification factors and other subgroups. Secondary endpoints of overall survival, recurrence-free survival, and distant disease–free survival consistently favored ribociclib. Ribociclib 400 mg showed a favorable safety profile with no new signals.

Conclusions

Ribociclib added to standard-of-care ET demonstrated a statistically significant, clinically meaningful improvement in iDFS with a well-tolerated safety profile. These data support ribociclib+ET as the treatment of choice in a broad population of patients with stage II or III HR+/HER2− EBC, including patients with N0 disease.