Combining abemaciclib with hormonal therapy reduces the risk of cancer recurrence by 25% in patients with high-risk early hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer, interim analysis of a phase III study presented at the 2020 European Society for Medical Oncology (ESMO) conference has suggested.
According to the authors, this was the first time in more than 20 years that there had been “an advance in the adjuvant treatment of this form of breast cancer”.
The open-label, randomised phase III trial, called monarchE, investigated the addition of abemaciclib to standard adjuvant endocrine therapy in patients with HR+, HER2- breast cancer, who were likely to experience recurrence in the first five years of their disease.
In the trial, which was funded by Eli Lilly, 5,637 patients were randomly assigned to either abemaciclib (150mg twice daily), plus endocrine therapy, or endocrine therapy alone. Patients were treated for a two-year treatment period or until they met the criteria for discontinuation. After the treatment period, all patients then continued endocrine therapy for five or ten years, as clinically indicated.
Abemaciclib is an approved cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor in HR+, HER2- advanced breast cancer with clinical efficacy both as monotherapy and in combination with endocrine therapy.
Overall, 11.3% of patients in the control group had a relapse of their cancer compared with 7.8% of those in the abemaciclib group, an absolute difference of 3.5%, which translated to a 25.3% reduction in risk.
This, the researchers said, was “a clinically meaningful result”. In addition, among the 43.5% of patients who were premenopausal at diagnosis, there was a 37% reduction in the risk of recurrence relative to endocrine therapy alone.
“Many of these patients can be cured with currently available treatments: surgery, radiotherapy, chemotherapy and hormone treatment. But about 20% have high-risk disease and will develop a recurrence either locally in the breast or elsewhere in the body over the first ten years of treatment,” said Stephen Johnston, lead author of the study and a consultant oncologist at the Royal Marsden Hospital NHS Foundation Trust in London.
“These patients with high-risk early breast cancer show a degree of resistance to hormone therapy, relapsing early despite everything we currently give them,” said Johnston.
“CDK4/6 inhibitors, such as abemaciclib, have transformed the way we treat metastatic breast cancer over the last few years, overcoming primary endocrine resistance and improving survival. So, it was an obvious step to see whether adding abemaciclib to hormone treatment in patients with high-risk early breast cancer could reduce the risk of their cancer returning.”
Giuseppe Curigliano, associate professor of medical oncology at the University of Milan, Italy, and chair of the ESMO Guidelines Committee, said the findings of the trial would “change practice”.
“Once approved for high risk HR+ HER2- early breast cancer the new standard of care for these patients will be to add two years of abemaciclib to endocrine therapy,” he said.
The most frequently reported adverse event in the abemaciclib arm was diarrhoea, which was managed with anti-diarrhoeal medication and dose adjustments.