The evidence supporting this protocol is provided by an open-label, multi-centre, phase III trial (monarchE) that investigated standard adjuvant endocrine therapy (ET) with/without abemaciclib after completion of surgery, radiation therapy and chemotherapy in patients with high-risk hormone receptor positive, HER-2 negative invasive early breast cancer. High-risk feature was defined based on presence of ≥4 positive pathologic axillary lymph nodes or 1-3 positive axillary lymph nodes with at least one of the following: tumour size >5cm, histological grade 3, or centrally assessed Ki-67 ≥20%.r
Between July 2017 and August 2019, 5637 patients were randomised 1:1 to receive ET either with abemaciclib (150 mg PO twice daily for 2 years) (n=2808) or with placebo (n=2829).r
The primary endpoint was invasive disease free survival (IDFS), and secondary end points included distant relapse-free survival (DRFS), overall survival (OS) and safety.r
Efficacy
After a median follow up of 27 months, there were 232 (8.2%) IDFS events in the abemaciclib plus ET group and 333 (11.8%) in the ET alone group (HR=0.70; 95% CI, 0.59-0.82; p < 0.0001). 3-year DRFS rates were 90.3% in the abemaciclib plus ET arm and 86.1% in the control arm (HR=0.69; 95% CI, 0.57-0.83; p < 0.0001).r
OS data remained immature, however at the first interim analysis there were 39 (1.4%) deaths observed in the abemaciclib arm and 37 (1.3%) observed in the control arm.r
Kaplan-Meier curve of IDFS in the intent-to-treat (ITT) populationr
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Kaplan-Meier curve of DRFS in the intent-to-treat (ITT) populationr
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Toxicity
A summary of the toxicities associated with this protocol are included in the table below. Overall, a higher incidence of grade ≥3 and serious toxicities were observed with abemaciclib plus ET vs ET alone (50% vs 16%; and 15% vs 9%, respectively). The most clinically significant toxicities (>30%) for this treatment were diarrhoea, neutropaenia, fatigue, leukopaenia and abdominal pain. Treatment discontinuation due to toxic events occurred in 6.5% of patients in the treatment arm vs 1.1% in the control arm.r At the time of interim analysis, there were 11 treatment-related deaths in the treatment arm as compared with 7 in the control arm.r
Adverse eventsr
aOne Grade 5 event occurred, bMax Grade 3 event (according to CTCAE v. 4),cMax Grade 2 event (according to CTCAE v. 4), Abbreviations: ET=endocrine therapy; n=number of patients; N=number of patients in population; NA=not applicable; PE=pulmonary embolism
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