# NATALEE

Source: https://onco.cc/trials/natalee/  
OnCo record `natalee` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Extended CDK4/6 inhibitors to a broad group of early hormone-positive breast cancer patients, including node-negative.

## Summary

NATALEE, trial NCT03701334 sponsored by Novartis and published in the New England Journal of Medicine in 2023, extended adjuvant CDK4/6 inhibitors to a broad group of stage II to III HR-positive, HER2-negative early breast cancer patients, including those with node-negative disease. It randomised 5,101 patients to three years of ribociclib plus a non-steroidal aromatase inhibitor or the aromatase inhibitor alone, met its primary invasive disease-free survival endpoint at three years with the benefit growing at four years, and led to approval in September 2024. OnCo links it to HR-positive breast cancer, ribociclib, Gabriel N. Hortobagyi, Dennis J. Slamon, the bottleneck of dormant cells and the monarchE and NATALEE papers. Whether three years of a costly drug is justified in lower-risk patients is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-04
- Registry id: NCT03701334
- Phase: 3
- Setting: Adjuvant ribociclib 3 years + endocrine therapy in stage II-III HR+/HER2- breast cancer
- Sponsor: Novartis
- Enrolled: 5101
- Result: iDFS HR 0.75.
- Outcomes: Invasive disease-free survival at 3 years: Ribociclib + NSAI 90.4% vs NSAI alone 87.1%, HR 0.75; Invasive disease-free survival at 4 years: Ribociclib + NSAI 88.5% vs NSAI alone 83.6%, HR 0.715
- Replication: Consistent with monarchE (abemaciclib) in a broader, lower-risk population; PALLAS and PENELOPE-B (palbociclib) were negative, so the effect is not a uniform class effect.

## Sources

- ClinicalTrials.gov NCT03701334: https://clinicaltrials.gov/study/NCT03701334

## Connected records

- cancers: [High-risk early HR-positive breast cancer](https://onco.cc/cancers/hr-positive-early-high-risk/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/)
- technologies: [CDK4/6 inhibitors](https://onco.cc/technologies/cdk46-inhibitor/)
- drugs: [Ribociclib](https://onco.cc/drugs/ribociclib/)
- companies: [Novartis](https://onco.cc/companies/novartis/)
- people: [Dennis J. Slamon](https://onco.cc/people/dennis-slamon/), [Gabriel N. Hortobagyi](https://onco.cc/people/gabriel-hortobagyi/)
- key papers: [monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer](https://onco.cc/key-papers/paper-monarche-jco-2020/), [NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer](https://onco.cc/key-papers/paper-natalee-nejm-2024/), [Ribociclib Plus Endocrine Therapy in Hormone Receptor-Positive/ERBB2-Negative Early Breast Cancer: 4-Year Outcomes From the NATALEE Randomized Clinical Trial](https://onco.cc/key-papers/paper-natalee-jama-oncol-2025-update/)
- terms: [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Surrogate endpoint validation: which stand-ins have earned trust](https://onco.cc/terms/surrogate-validation/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- roadmaps: [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/)

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