Prospects of eribulin administration for patients with HR-positive HER2-negative metastatic breast cancer after progression on CDK4/6 Inhibitors: theoretical background and first experience

Abstract

Combining cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors with endocrine therapies in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in the first and second lines has emerged as optimal treatment strategy and has implications related to clinical efficacy, rapid clinical response and manageable tolerability. However, approximately one in five women has progression during the first year, we have to make efforts to choose the treatments for hormone receptor-positive breast cancer. Potential treatment options include prospective chemotherapy drug eribulin, its efficacy has been demonstrated in various biological subtypes of metastatic breast cancer in patients pretreated with anthracyclines and taxanes. Data from EMPOWER study evaluating the use of eribulin in female patients with hormone positive HER2-negative metastatic breast cancer who received CDK 4/6 inhibitor therapy showed promising results. In the cohort eribulin was prescribed according to the FDA indications in the USA after at least three prior regimens with a prior anthracycline and a taxane overall response rate was 26.7%, clinical benefit rate was 54.1%, median progressive-free survival was not reached and 6-month progressive-free survival rates was 70.4%. Eribulin demonstrated a manageable tolerability profile, adverse event rates were similar to those in clinical trials and other observational studies. In this paper we present the analysis from Russia of five cases of luminal HER2-negative breast cancer who had progression after CDK 4/6 inhibitor therapy. All patients had visceral metastases, one of them had brain metastases. Eribulin was used according to prescribing information in Russia, in metastatic settings in patients pretreated with anthracyclines and taxanes in the second chemotherapy line (3 patients) and in the third line (2 patients). Four patients achieved stable disease, one patient had partial response. Duration of eribulin treatment response was from 8 to 22 months. Eribulin appeared to be well-tolerated, dose reduction was not noted. Data from EMPOWER (USA) and the first treatment results from Russia demonstrated eribulin may be a potential treatment option in hormone-positive breast cancer following prior CDK 4/6i therapy for disease control and to preserve quality of life.

Keywords

• advanced breast cancer
• hormonal therapy with cdk 4/6 inhibitors
• hormone resistance
• eribulin chemotherapy