Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: The monarchE trial has demonstrated a significant improvement in invasive disease-free survival (IDFS) with the use of abemaciclib alongside endocrine therapy (ET) among high-risk patients with hormone receptor (HR)-positive, HER2-negative early breast cancer.
Stephen Johnston, from The Royal Marsden NHS Foundation Trust in London, UK, told delegates at the ESMO Virtual Congress 2020 that abemaciclib is the first oral CDK 4/6 inhibitor to demonstrate an improvement in IDFS in this patient population when added to standard of care ET.
“Results indicate the prevention of early recurrence and a reduction in the risk of distant recurrence (metastatic disease) by a clinically meaningful 28.3%”, he said.
Following the approval of abemaciclib for HR-positive, HER2-negative advanced breast cancer, the investigators hypothesised the inhibitor could be beneficial in women or men with early disease features associated with a high-risk of distance recurrence, such as four or more positive axillary nodes, or one to three positive nodes plus a tumour at least 5 cm in size, grade 3 histology, or a Ki67 score of 20% or more.
At the time of analysis, median follow-up was around 15.5 months for both the 2808 patients randomly assigned to receive abemaciclib 150 mg twice daily for up to 2 years plus 5–10 years of standard of care ET, and the 2829 patients given only ET.
Therefore, over 70% of patients were still within the first 2 years of treatment, the presenter explained.
Nevertheless, abemaciclib-treated patients were significantly less likely to experience invasive recurrence than controls, with a hazard ratio of 0.747, and 2-year rates of IDFS of 92.2% versus 88.7%: a 3.5% absolute difference.
Distant relapse-free survival also favoured abemaciclib plus ET use, with a significant hazard ratio of 0.717 versus ET alone, and 2-year rates of 93.6% versus 90.3%, translating to a 3.3% absolute difference.
Of note, the greatest reductions in distant recurrence in the abemaciclib arm were noted in the bones and liver.
Stephen Johnston said that 16.6% of the abemaciclib arm discontinued treatment because of adverse events (AEs) but 66% of these patients continued to take ET, whereas just 0.8% of controls discontinued ET.
Median duration of ET in the intervention and control arms was 14.9 and 15.2 months, respectively, and the median duration of abemaciclib was 14.0 months, but this “will continue to increase”, the presenter said.
Discussing treatment-emergent AEs, Stephen Johnston highlighted the rate of diarrhoea, which affected 82.8% of abemaciclib-treated patients, including 7.6% at grade 3, whereas just 7.1% of controls experienced this side effect and just 0.1% at grade 3.
However, further analysis showed that “diarrhoea frequency and severity decreases significantly over time”, he said, with most patients managing the side effect with medication and dose adjustments.
Other AEs of interest included a trend towards a higher rate of venous thromboembolism with abemaciclib plus ET than ET alone (2.3 vs 0.5%), including pulmonary embolism (0.9 vs 0.1%), as well as interstitial lung disease (2.7 vs 1.2%) and febrile neutropenia (0.3 vs <0.1%).
In addition, patients using abemaciclib plus ET experienced a significant reduction in both arthralgia and hot flush compared with those given only ET, which Stephen Johnston and co-investigators describe in the linked article in the Journal of Clinical Oncology as an “intriguing observation [that] has previously been reported for a CDK4/6 inhibitor plus ET.”
LBA5_PR - Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib in high risk early breast cancer. Ann Oncol 2020; 31 (Suppl 4): S1142–S1215. DOI:10.1016/annonc/annonc325.
Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol; Published online 20 September 2020. DOI: 10.1200/JCO.20.02514.
Wolff AC. CDK4/6 Inhibition in Early-Stage Breast Cancer: The New Standard? J Clin Oncol; Published online 20 September 2020. DOI: 10.1200/JCO.20.02688.
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