Cancer Treatment Today

Ribociclib has demonstrated a statistically significant overall survival benefit in pre- and postmenopausal
patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2)
advanced breast cancer. New Adjuvant Trial with Ribociclib [LEE011] (NATALEE) is a trial evaluating the
efficacy and safety of adjuvant ribociclib plus endocrine therapy (ET) versus ET alone in patients with
HR+/HER2 early nonmetastatic breast cancer (EBC).
“NATALEE is a multicenter, randomized, open-label, Phase III trial in patients with HR+/HER2 EBC. Eligible
patients include women, regardless of menopausal status, and men aged 18years. Select patients with stage IIA,
stage IIB, or stage III disease (per the anatomic classification in the AJCC Cancer Staging Manual, 8th edition)
with an initial diagnosis 18months prior to randomization are eligible. Patients receiving standard (neo)adjuvant
ET are eligible if treatment was initiated 12months before randomization. Patients undergo 1:1 randomization to
ribociclib 400mg/day (3weeks on/1week off) +ET (letrozole 2.5mg/day or anastrozole 1mg/day [investigator’s
discretion] plus goserelin [men or premenopausal women]) or ET alone. Ribociclib treatment duration is
36months; ET treatment duration is 60months. The primary end point is invasive disease-free survival. The 36-
month treatment duration of ribociclib in NATALEE is extended compared with that in other adjuvant cyclin-
dependent kinases 4 and 6 (CDK4/6) inhibitor trials and is intended to maximize efficacy due to longer duration
of CDK4/6 inhibition. Compared with the 600-mg/day dose used in advanced breast cancer, the reduced
ribociclib dose used in NATALEE may improve tolerability while maintaining efficacy. NATALEE includes
the broadest population of patients with HR+/HER2 EBC of any Phase III trial currently evaluating adjuvant therapy. The Natalee trial published by Slamon et al established efficacy in the adjuvant setting ofr early breast cancer and the emerging consensus that this large phase III trial changes the standard of care.

Alkabban, F.M., Ferguson, T. (2022). Breast Cancer. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure
Island
(FL):
StatPearls
Publishing;
2024
Jan-.
Available
from:

https://www.ncbi.nlm.nih.gov/books/NBK482286/

Rascon, K., Flajc, G., De Angelis, C., Liu, X., Trivedi, M. V., & Ekinci, E. (2019). Ribociclib in HR+/HER2-
Advanced or Metastatic Breast Cancer Patients. The Annals of pharmacotherapy, 53(5), 501–509.

https://doi.org/10.1177/1060028018817904

RE: LISA SINKOVICH«@Claimant»
NMR #: 1092231
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Slamon, D. J., Fasching, P. A., Hurvitz, S., Chia, S., Crown, J., Martín, M., Barrios, C. H., Bardia, A., Im, S. A.,
Yardley, D. A., Untch, M., Huang, C. S., Stroyakovskiy, D., Xu, B., Moroose, R. L., Loi, S., Visco, F., Bee-
Munteanu, V., Afenjar, K., Fresco, R., Hortobagyi, G. N. (2023). Rationale and trial design of NATALEE: a
Phase III trial of adjuvant ribociclib+endocrine therapy versus endocrine therapy alone in patients with
HR+/HER2- early breast cancer. Therapeutic advances in medical oncology, 15, 17588359231178125.

https://doi.org/10.1177/17588359231178125

Slamon DJ, Stroyakovskiy D, Yardley DA, et al: Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2– early breast cancer. 2023 ASCO Meeting. Abstract LBA500. Presented June 2, 2023.