Clinical trialPhase 3Breast cancer

Adjuvant Abemaciclib Plus Endocrine Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, High-Risk Early Breast Cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes

J Clin Oncol · 20245637 patients (whole trial)

Rastogi P, O'Shaughnessy J, Martin M, Boyle F, Cortes J, Rugo HS, et al. J Clin Oncol. 2024. 42:987-993

A newer report of this study has been published: Overall survival with abemaciclib in early breast cancer (2026)

Study type: Clinical trial
Study name: monarchE
Phase: Phase 3
Design: Open-label randomised trial (updated report of the clinical trial)
Sample size: 5637 patients (whole trial)
Source: J Clin Oncol · 2024
Trial registration: NCT03155997

In plain words

In hormone-positive, HER2-negative breast cancer that has spread to several lymph nodes and has a high risk of coming back, adding abemaciclib tablets for two years to standard hormone therapy lowered the risk of the cancer returning by about one third, and this benefit kept growing even years after the drug was stopped. Diarrhoea is the most common side effect and can usually be controlled with anti-diarrhoea medicines and dose adjustment.

Key results

HR 0.680

IDFS (median follow-up 54 months)

95% CI 0.599–0.772

HR 0.675

DRFS

95% CI 0.588–0.774

7.6%

Absolute IDFS improvement at 5 years

Versus 6% at 4 years and 4.8% at 3 years

6.7%

Absolute DRFS improvement at 5 years

208 vs 234

Deaths

Overall survival has not yet reached statistical significance

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 + 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.

2Endocrine therapy alone

Standard endocrine therapy of physician's choice per label.

Source of the regimen details: ClinicalTrials.gov NCT03155997 (150 mg twice daily for up to 2 years)

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.

Endpoints

Primary outcome: invasive disease-free survival (IDFS). Secondary: distant relapse-free survival (DRFS), overall survival and safety.

Safety and side effects

No new safety signals were seen in this analysis. Diarrhoea, neutropenia and fatigue are known adverse effects of abemaciclib, and venous thromboembolism is also listed in the label; details are in the full text of the original paper.

Clinical significance and place in guidelines

The FDA approved adjuvant abemaciclib in 2021 and removed the Ki-67 restriction in 2023. ESMO guideline (Pan-Asian adapted version 2024): 2 years of abemaciclib with endocrine therapy after completion of locoregional treatment should be considered in patients with stage III or high-risk stage II disease [I, A]. Olaparib and abemaciclib should not be given concurrently, but sequential use (olaparib first) may be considered [V, A].

Limitations

Open-label design; overall survival is not yet significant; only high-risk node-positive patients were enrolled.

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.