Clinical trialPhase 3Breast cancer

Overall survival with abemaciclib in early breast cancer

Ann Oncol · 20265637 patients (2808 in the abemaciclib plus endocrine therapy group and 2829 in the endocrine therapy alone group)

Johnston S, Martin M, O'Shaughnessy J, Hegg R, Tolaney SM, Guarneri V, et al. Ann Oncol. 2026. 37:155-165

Study type: Clinical trial
Study name: monarchE
Phase: Phase 3
Design: Open-label randomised trial — primary overall survival report
Sample size: 5637 patients (2808 in the abemaciclib plus endocrine therapy group and 2829 in the endocrine therapy alone group)
Source: Ann Oncol · 2026
Trial registration: NCT03155997

In plain words

In this large study, women and men with hormone receptor-positive, HER2-negative breast cancer that had reached the lymph nodes and had a high risk of coming back either took abemaciclib tablets for two years after surgery on top of their usual hormone therapy, or had hormone therapy alone. After about six years of follow-up, adding abemaciclib not only made the cancer come back less often but also lowered the risk of death by about 16%. Decisions about treatment should be made with the treating doctor.

Key results

0.842 (95% CI 0.722–0.981)

Overall survival (HR)

P=0.027; 661 deaths; median follow-up 76.2 months; prespecified significance boundary met

86.8% vs 85.0%

7-year overall survival

Absolute difference 1.8%

77.4% vs 70.9%

7-year invasive disease-free survival

Absolute difference 6.5%; HR 0.734 (0.657–0.820)

80.0% vs 74.9%

7-year distant relapse-free survival

Absolute difference 5.1%; HR 0.746 (0.662–0.840)

6.4% vs 9.4%

Alive with metastatic disease

In addition to patients who had died of metastatic disease

Drugs in this study:Abemaciclib (Verzenio)Tamoxifen (Nolvadex)

Dose and schedule cards

Abemaciclib + hormone therapy (monarchE)

HR-positive/HER2-negative, node-positive, high risk: 4 or more involved lymph nodes, or 1 to 3 nodes with grade 3 or a tumour size of 5 cm or moreCycle length: ContinuousOn the page “Breast cancer” · Early hormone receptor-positive disease: hormone therapy ± CDK4/6 inhibitor

HR-positive/HER2-negative, node-positive, high risk: 4 or more involved lymph nodes, or 1 to 3 nodes with grade 3 or a tumour size of 5 cm or more

Drug	Dose	Route	Schedule
Abemaciclib	150 mg twice daily	Oral	Continuous
Tamoxifen or an aromatase inhibitor	Standard dose	Oral	Continuous

Cycle length: Continuous
Duration: Abemaciclib for 2 years; hormone therapy continues

Monitoring: blood counts and liver tests before starting, every 2 weeks for the first 2 months, monthly for the next 2 months and then as clinically indicated. Venous thromboembolism: in early disease, discontinue for VTE of any grade. Severe hepatic impairment: reduce the dosing frequency to once daily.

On the page “Breast cancer” · Early hormone receptor-positive disease: hormone therapy ± CDK4/6 inhibitor

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Abemaciclib plus endocrine therapy

Abemaciclib 150 mg orally twice daily (at least 6 hours apart) for up to 2 years or until recurrence, with standard endocrine therapy of physician's choice (tamoxifen or an aromatase inhibitor per label) for at least 5 years.

2Endocrine therapy alone

Standard endocrine therapy of physician's choice (per label) for at least 5 years.

Source of the regimen details: ClinicalTrials.gov NCT03155997 and the FDA label for Verzenio (DailyMed, sections 2 and 14.1)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence. Cohort 1: 4 or more positive axillary lymph nodes, or 1 to 3 nodes with grade 3 or tumour size 50 mm or more; cohort 2: 1 to 3 nodes with Ki-67 ≥20% (without cohort 1 criteria).

Endpoints

Primary endpoint of the trial: invasive disease-free survival (IDFS). This paper reports the primary overall survival results (key secondary endpoint) and updated estimates of IDFS and distant relapse-free survival (DRFS).

Safety and side effects

According to the abstract, long-term safety data showed no concern for late toxicity. Adverse event details are in the full text.

Clinical significance and place in guidelines

This is the first report of a significant overall survival improvement with a CDK4/6 inhibitor in the adjuvant treatment of early breast cancer, and it strengthens the place of 2 years of abemaciclib with endocrine therapy in HR-positive/HER2-negative, node-positive, high-risk patients.

Limitations

The trial was open-label (no placebo), and the absolute overall survival difference at 7 years is small (1.8%). Adverse event details and subgroup analyses are in the full text.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.