Clinical trialPhase 3Breast cancer

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer

JCO · 2017493 patients

Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, et al. JCO. 2017. 35:3638-3646

Study type: Clinical trial
Study name: MONARCH 3
Phase: Phase 3
Design: Randomised, double-blind phase 3 trial (abemaciclib or placebo plus a non-steroidal aromatase inhibitor)
Sample size: 493 patients
Source: JCO · 2017

In plain words

In this study, women past menopause with advanced hormone receptor-positive breast cancer who had not yet had any whole-body treatment for advanced disease received either the drug abemaciclib or a placebo (dummy pill), together with a hormone drug (anastrozole or letrozole). Adding abemaciclib clearly lengthened the time the disease stayed under control without getting worse and made tumours shrink more often. The most common side effect was diarrhoea, which was mostly mild, but a drop in white blood cells (neutropenia) was also more common in this group.

Key results

HR 0.54 (95% CI 0.41–0.72)

Progression-free survival (PFS)

P = 0.000021

Not reached (abemaciclib) vs 14.7 months (placebo)

Median PFS

59% vs 44%

Objective response rate (patients with measurable disease)

P = 0.004

Drugs in this study:Abemaciclib (Verzenio)Fulvestrant (Faslodex)Letrozole (Femara)Palbociclib (Ibrance)Anastrozole (Arimidex)Ribociclib (Kisqali)

Dose and schedule cards

Hormone therapy + CDK4/6 inhibitor (PALOMA-2, MONALEESA-2, MONARCH 3; after progression: PALOMA-3)

Advanced HR-positive/HER2-negative disease; first-line with an aromatase inhibitor, or with fulvestrant after prior hormone therapyOn the page “Breast cancer” · Advanced hormone receptor-positive / HER2-negative disease

Advanced HR-positive/HER2-negative disease; first-line with an aromatase inhibitor, or with fulvestrant after prior hormone therapy

Drug	Dose	Route	Schedule
One of three drugs
Palbociclib	125 mg once daily	Oral	Days 1–21
Ribociclib	600 mg once daily	Oral	Days 1–21
Abemaciclib	150 mg twice daily	Oral	Continuous
Combined with
Letrozole (or anastrozole 1 mg)	2.5 mg once daily	Oral	Continuous
Or combined with
Fulvestrant	500 mg (two 5-mL injections, one in each buttock)	IM, slowly	Days 1, 15 and 29, then monthly

Cycle length: Palbociclib and ribociclib: every 28 days; abemaciclib continuous
Duration: Until progression or unacceptable toxicity

Ribociclib: reduce to 400 mg and then 200 mg. Abemaciclib: monotherapy 200 mg twice daily.

On the page “Breast cancer” · Advanced hormone receptor-positive / HER2-negative disease

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 + non-steroidal aromatase inhibitor

Abemaciclib 150 mg twice daily on a continuous schedule, plus anastrozole 1 mg or letrozole 2.5 mg daily.

2Placebo + non-steroidal aromatase inhibitor

Placebo (150 mg twice daily on a continuous schedule) plus anastrozole 1 mg or letrozole 2.5 mg daily.

Source of the regimen details: Abstract of the paper

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

Postmenopausal women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer who had received no prior systemic therapy in the advanced setting.

Endpoints

Primary objective: investigator-assessed progression-free survival (PFS). Secondary objectives included response and safety. The planned interim analysis was performed after 189 events.

Safety and side effects

In the abemaciclib arm, diarrhoea was the most frequent adverse event (81.3%) but was mainly grade 1 (44.6%). The most frequent grade 3 or 4 adverse events (abemaciclib versus placebo) were neutropenia (21.1% versus 1.2%), diarrhoea (9.5% versus 1.2%) and leucopenia (7.6% versus 0.6%).

Clinical significance and place in guidelines

Based on the abstract, abemaciclib plus a non-steroidal aromatase inhibitor as first-line therapy for HR-positive, HER2-negative advanced breast cancer improved progression-free survival and response rate, with tolerable safety. Regulatory approvals and guideline recommendations should be checked separately.

Limitations

Results are from the planned interim analysis after 189 events, and median PFS in the abemaciclib arm had not yet been reached. The primary endpoint was investigator-assessed. Overall survival data 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.