Clinical trialPhase 3Breast cancer

Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE)

JCO · 20205,637 patients

Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, et al. JCO. 2020. 38:3987-3998

Study type: Clinical trial
Study name: monarchE
Phase: Phase 3
Design: Open-label randomised trial with 1:1 allocation
Sample size: 5,637 patients
Source: JCO · 2020

In plain words

In this large study, women and men with high-risk, hormone-positive early breast cancer were given the oral drug abemaciclib for 2 years after surgery, on top of their usual hormone therapy. Adding this drug lowered the risk of the disease coming back: after 2 years, about 92.2% of patients in the abemaciclib group were free of invasive recurrence, compared with 88.7% in the hormone-therapy-only group. The drug's side effects were the ones already known. The decision to use this drug should be made with the treating doctor.

Key results

HR 0.75 (95% CI 0.60–0.93)

Invasive disease-free survival (IDFS)

P = 0.01; 323 IDFS events in the intention-to-treat (ITT) population at the prespecified interim analysis

92.2% vs 88.7%

2-year IDFS rate

Abemaciclib plus endocrine therapy vs endocrine therapy alone

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

Standard-of-care adjuvant endocrine therapy with abemaciclib 150 mg twice daily for 2 years.

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

2Endocrine therapy alone

Standard-of-care adjuvant endocrine therapy alone.

Standard endocrine therapy of physician's choice per label.

Source of the regimen details: Abstract of the paper, ClinicalTrials.gov NCT03155997 (150 mg twice daily at least 6 hours apart, 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 high-risk HR-positive, HER2-negative early breast cancer who had undergone surgery and, when indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Eligible patients had four or more positive lymph nodes, or one to three positive nodes with one of the following: tumour size 5 cm or more, histological grade 3, or central Ki-67 20% or higher.

Endpoints

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

Safety and side effects

Safety data were consistent with the known safety profile of abemaciclib. Exact rates of grade 3 or higher adverse events are not reported in the abstract.

Clinical significance and place in guidelines

This study showed that adding abemaciclib to adjuvant endocrine therapy significantly improves IDFS in high-risk node-positive HR-positive, HER2-negative patients, and it is the first CDK4/6 inhibitor with such a result in the adjuvant setting. The abstract does not mention regulatory approvals or guideline recommendations; current approval and guideline status should be checked separately. Overall survival data from this interim analysis are not reported in the abstract.

Limitations

This report is based on a preplanned interim analysis, and the study design was open-label. Long-term overall survival data and longer follow-up are not reported in the abstract.

Original article (DOI)PubMed

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.