A study on the treatment of patients with locally advanced or metastatic HER2-positive breast cancer using a combination therapy consisting of the new drug giredestrant, trastuzumab, and pertuzumab.

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue characterized by the uncontrolled proliferation of breast cells. Treatment depends on various factors, such as the patient’s overall health, the tumor stage (locally confined or metastatic), the tumor growth rate (Ki-67 index), as well as the presence of hormone receptors (estrogen and progesterone receptor-positive) and/or the presence of the HER2 receptor on the tumor cells. For HER2-positive breast cancer, targeted drugs are used that recognize and specifically attack the HER2 receptor, including trastuzumab and pertuzumab. Phesgo is an approved drug that combines trastuzumab and pertuzumab. Hormone receptor-positive breast cancer is treated with anti-hormone therapy. Various classes of drugs are available for this purpose: aromatase inhibitors (e.g., letrozole), selective estrogen receptor modulators (SERMs, e.g., tamoxifen), or selective estrogen receptor degraders (SERDs, e.g., fulvestrant). Premenopausal women often receive additional so-called LHRH agonists to suppress the body’s increased production of hormones. For breast cancer that is both HER2-positive and hormone receptor-positive, these two treatment approaches are frequently combined. Giredestrant belongs to the SERD class but has not yet been approved.

In the locally advanced stage (Stage 3) or in cases of detectable metastases (Stage 4), a cure is generally no longer possible. In these cases, palliative treatment is used to slow the progression of the disease. In the first phase of treatment, chemotherapy (e.g., docetaxel, paclitaxel) is often combined with pertuzumab and trastuzumab (Phesgo). This is followed by maintenance therapy to prolong the effects of the initial treatment and delay disease progression. This therapy is usually continued until the tumor disease eventually progresses. Phesgo is typically used in combination with anti-hormone therapy for this purpose.

The goal of the heredERA study is to investigate whether maintenance therapy with Phesgo and giredestrant is superior to Phesgo monotherapy. As part of the study, patients will be randomly assigned to two groups. The control group receives standard therapy with Phesgo and an individually selected anti-hormone therapy; for women before or during menopause, this includes additional treatment with LHRH analogs. The experimental group receives the new drug giredestrant as anti-hormonal therapy in combination with Phesgo as part of maintenance therapy. The duration of treatment depends on the response to therapy and the tolerability of the medications. Follow-up will continue until the disease progresses. The primary observation period is planned to last at least four years, but no longer than ten years. Assignment is open-label, meaning that patients and their treating physicians know which study group they are in.

Women and men aged 18 and older with hormone receptor-positive, HER2-positive breast cancer may participate in the study if the disease is locally advanced (Stage 3) or metastatic (Stage 4) and cannot be surgically removed (inoperable). Previous treatment may consist only of Phesgo and a maximum of one anti-hormone therapy, provided that this did not include a SERD (e.g., fulvestrant). In addition, patients must not have active brain metastases. Men and women of childbearing age must use a reliable method of contraception during treatment and for up to seven months after the last dose of Phesgo.