Ribociclib Shows Overall Survival Benefit at 6 Years in NATALEE Breast Cancer Trial

Adjuvant ribociclib (Kisqali; Novartis) plus a nonsteroidal aromatase inhibitor (NSAI) showed an overall survival (OS) benefit compared with an NSAI alone in patients with high-risk hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative early breast cancer, according to 6-year results from the phase 3 NATALEE trial (NCT03701334).¹

The findings, presented at the European Society for Medical Oncology (ESMO) Congress 2026 and published in Annals of Oncology, showed a 19.1% relative reduction in the risk of death with ribociclib plus endocrine therapy (hazard ratio [HR], 0.809; 95% CI, 0.661-0.989). The estimated absolute difference in OS at 6 years was 2.1 percentage points.¹

The OS analysis was prespecified and descriptive, with a nominal one-sided P value of .019. Invasive disease-free survival (iDFS), the trial’s primary end point, had previously demonstrated a statistically significant benefit.^1,2

A Broader High-Risk Early Breast Cancer Population

NATALEE enrolled 5101 adults with HR-positive, HER2-negative early breast cancer. Eligible patients had anatomic stage IIA disease with lymph node involvement or additional high-risk features, stage IIB disease, or stage III disease. The population included patients with node-positive disease and selected patients with high-risk node-negative disease.^1,2

Participants were randomly assigned to receive ribociclib plus an NSAI or an NSAI alone. Ribociclib was administered at 400 mg daily for 3 weeks, followed by 1 week off, for up to 3 years. Patients in both groups received letrozole or anastrozole for at least 5 years. Premenopausal women and men also received goserelin.^1,3

The inclusion of selected patients without nodal involvement is relevant when discussing treatment options, although node-negative status alone did not qualify patients for the trial. Eligibility depended on tumor stage and other risk characteristics.¹

Survival and Recurrence Benefits at 6 Years

At a median OS follow-up of 66.5 months, the estimated absolute OS difference between treatment groups increased from 1.2 percentage points at 5 years to 2.1 percentage points at 6 years, according to Novartis.^1,4 The relative reduction reflected by the hazard ratio should be distinguished from the smaller absolute difference in estimated survival at the 6-year time point.

The iDFS benefit also continued with longer follow-up. At 6 years, the absolute difference was 5.3 percentage points in favor of ribociclib plus endocrine therapy (HR, 0.741; 95% CI, 0.646-0.849). The findings were generally consistent across key subgroups.¹

Results for distant disease-free survival also favored the combination (HR, 0.744; 95% CI, 0.646-0.858). The company reported a 4.9-percentage-point absolute difference at 6 years.^1,4

The longer follow-up is particularly relevant in HR-positive early breast cancer, where recurrence remains a concern after initial treatment. The NATALEE findings suggest that the benefit of adding ribociclib persists beyond the planned 3-year treatment period.^1,2

The authors reported no new safety signals in the 6-year analysis. Novartis reported secondary primary malignancies in 3.0% of patients receiving ribociclib plus endocrine therapy and 3.3% of those receiving endocrine therapy alone.^1,4

Monitoring Makes Pharmacist Follow-Up Essential

Ribociclib is FDA approved with an aromatase inhibitor as adjuvant treatment for adults with HR-positive, HER2-negative stage II or III early breast cancer at high risk of recurrence. The recommended early breast cancer starting dose is 400 mg once daily for 21 consecutive days, followed by 7 days off, for 3 years or until recurrence or unacceptable toxicity.³

Pharmacists can help patients understand the repeating schedule and distinguish it from the continuous aromatase inhibitor regimen. If a dose is missed or the patient vomits after taking it, the prescribing information advises against taking an additional dose that day; the next dose should be taken at the usual time.³

Laboratory and cardiac monitoring are central to safe treatment. The prescribing information recommends a complete blood count and liver function tests before treatment, every 2 weeks during the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. An electrocardiogram is recommended before treatment and at approximately day 14 of the first cycle. Electrolytes should be checked before treatment and at the beginning of each of the first 6 cycles.³

Pharmacists can review medications for agents that prolong the QT interval and strong CYP3A inhibitors, which the label advises avoiding with ribociclib. Counseling should also cover signs of infection, liver injury, and new or worsening respiratory symptoms, along with when to contact the oncology team.³

As patients consider years of adjuvant therapy, pharmacists can help connect the NATALEE results to the practical demands of treatment: regular monitoring, management of adverse effects, and continued endocrine therapy after ribociclib is completed.

REFERENCES

1. Slamon DJ, Hortobagyi GN, Stroyakovskiy D, et al. Overall survival with adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with high-risk HR+/HER2- early breast cancer: Six-year follow-up of the NATALEE trial. Ann Oncol. Published online October 23, 2026. doi:10.1016/j.annonc.2026.10.1288

2. Hortobagyi GN, Lacko A, Sohn J, 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. doi:10.1016/j.annonc.2024.10.015

3. Kisqali. Prescribing information. Novartis Pharmaceuticals Corporation; revised July 2026. Accessed October 27, 2026. https://www.novartis.com/us-en/sites/novartis_us/files/kisqali.pdf

4. Kisqali shows clinically meaningful overall survival in broadest HR+/HER2- early breast cancer population at high risk of recurrence. News release. Novartis. October 23, 2026. Accessed October 27, 2026. https://www.novartis.com/news/media-releases/kisqali-shows-clinically-meaningful-overall-survival-broadest-hrher2-early-breast-cancer-population-high-risk-recurrence