NATALEE: trial | Bending the Curve: Trial by Trial

NATALEE

Ribociclib plus endocrine therapy in early breast cancer

Population

HR-positive, HER2-negative early breast cancer of anatomical stage II or III (stage IIA with N0 required additional risk factors)

Design

International, open-label, randomized phase 3 trial (1:1) of ribociclib 400 mg per day (3 weeks on, 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor, or the aromatase inhibitor alone; premenopausal women and men also received goserelin

Primary endpoint

iDFS

Arms

Ribociclib plus NSAI (experimental, n = 2,549): Ribociclib 400 mg per day, 3 weeks on and 1 week off for 36 months, plus letrozole 2.5 mg or anastrozole 1 mg per day
NSAI alone (control, n = 2,552): Letrozole 2.5 mg or anastrozole 1 mg per day

People

Slamon D

iDFSHR 0.75 (95% CI 0.62–0.91)Δ 36-month iDFS+3.3 pointsiDFSHR 0.749 (95% CI 0.628–0.892)Δ 36-month iDFS+3.1 points

Show the numbers

Results reported for NATALEE
Endpoint	Analysis	Ribociclib plus NSAI	NSAI alone	Effect
iDFS	interimSlamon 2024	90.4% at 3 y	87.1% at 3 y	HR 0.75 (95% CI 0.62–0.91)P=0.003Prespecified interim analysis with 426 events; stopping boundary one-sided P of 0.0128.
iDFS	finalmedian follow-up 33.3 monthsHortobagyi 2025	90.7% at 3 y (89.3–91.8%)	87.6% at 3 y (86.1–88.9%)	HR 0.749 (95% CI 0.628–0.892)P=0.0012Final preplanned iDFS analysis; 226 and 283 iDFS events. Overall survival data immature.

Results reported for NATALEE
Endpoint	Analysis	Ribociclib plus NSAI	NSAI alone	Effect
iDFS	interimSlamon 2024	90.4% at 3 y	87.1% at 3 y	HR 0.75 (95% CI 0.62–0.91)P=0.003Prespecified interim analysis with 426 events; stopping boundary one-sided P of 0.0128.
iDFS	finalmedian follow-up 33.3 monthsHortobagyi 2025	90.7% at 3 y (89.3–91.8%)	87.6% at 3 y (86.1–88.9%)	HR 0.749 (95% CI 0.628–0.892)P=0.0012Final preplanned iDFS analysis; 226 and 283 iDFS events. Overall survival data immature.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
iDFS	0.75	0.62–0.91
iDFS	0.749	0.628–0.892

Appears in

2020 Adjuvant CDK4/6 inhibition: monarchE and NATALEE

Sources

Slamon D, Lipatov O, Nowecki Z, McAndrew N, Kukielka-Budny B, Stroyakovskiy D, et al. Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med. 2024;390(12):1080-1091.
PubMed DOI
Hortobagyi GN, Lacko A, Sohn J, Cruz F, Ruiz Borrego M, Manikhas A, et al. A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial. Ann Oncol. 2025;36(2):149-157.
PubMed DOI