A Study of Elacestrant, an anti-hormonal therapy, and Abemaciclib, a CDK-4/6 inhibitor, in patients with hormone receptor-positive, HER2-negative breast cancer and brain metastases

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue characterized by uncontrolled proliferation of mammary gland cells. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the tumor’s growth rate (Ki-67 index), detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased presence of the HER2 protein on the cells (HER2-positive). If the disease is advanced, metastases may occur throughout the body. In this case, the brain may also be affected. Proper treatment of these brain metastases is challenging, so new options for well-tolerated and effective therapy are being sought. In addition to traditional chemotherapy, targeted drugs are increasingly being used; these recognize specific structures on tumor cells and destroy them selectively. Abemaciclib and elacestrant are drugs from different classes of active ingredients that are used in combination due to their complementary effects. Abemaciclib is a CDK4/6 inhibitor that inhibits cell growth, while elacestrant targets the hormone receptor of the tumor cells. A key advantage of elacestrant compared to other hormone receptor-targeted drugs is its ability to penetrate the brain and thus act directly on the metastases.

The goal of the ELECTRA study is to investigate the combination of abemaciclib and elacestrant in breast cancer with brain metastases. The ELECTRA study is a single-arm Phase 1b/2 study, meaning that all participants receive the study medications. Additionally, the study is open-label, meaning that both the medical staff and the participants know which medications are being administered. Initially, a well-tolerated dose will be identified before that dosage is administered over the long term. The study will initially last one year and may run for up to three years, during which time tolerability and efficacy will be evaluated.

Women and men aged 18 and older who have hormone receptor-positive, HER2-negative breast cancer and at least one active brain metastasis are eligible to participate in the study. Treatment with corticosteroids and neurological symptoms caused by the brain metastasis should be stable. The advanced or metastatic disease should have already been treated with at least one hormone therapy, up to two courses of chemotherapy, and up to two CDK4/6 inhibitors—but not with abemaciclib. The last dose of fulvestrant should have been administered at least 42 days prior to the start of study treatment; other anti-hormonal therapies and chemotherapies must have been administered for the last time at least 14 days prior to the start of the study.