Comparison of fulvestrant monotherapy versus the combination of fulvestrant and capivasertib (neoadjuvant) in patients with lobular breast cancer at high risk of recurrence

Lobular breast cancer (invasive lobular carcinoma, ILC) is a malignant disease of the breast tissue characterized by the uncontrolled proliferation of cells in the lobules of the mammary glands. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the tumor’s growth rate (Ki-67 index), the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased presence of HER2 receptors on the cells (HER2-positive). The stage of the disease is also very important: While in the locally confined stage (stages 1–2A) the disease is limited to the breast and a cure is highly likely, the locally advanced stage (stages 2B–3B) means that the tumor is already larger or that lymph nodes are involved. As a rule, surgical removal of the tumor is the goal for cancers without metastases (spread to other organs). Hormone receptor-positive cancers can also be pretreated with anti-hormone therapy (e.g., fulvestrant). The goal of this treatment is to stop the growth of cancer cells and thereby shrink the tumor. Combining fulvestrant with capivasertib—a study drug that has already been approved—might be even more effective at stopping cell growth. Capivasertib is a so-called serine/threonine kinase inhibitor that can block various signaling pathways involved in cancer cell metabolism.

The goal of this Phase 2 study is to investigate the efficacy and safety of the combination therapy with capivasertib + fulvestrant compared to monotherapy with fulvestrant in a selected group of patients.

As part of the study, patients will be randomly assigned to 2 groups. Group 1 (treatment arm) will first receive capivasertib for over 2 weeks, followed by capivasertib plus fulvestrant for an additional 8 weeks. Group 2 (control arm) will receive only fulvestrant for 10 weeks. Before the start of treatment, the Ki-67 index (growth factor) in the tumor will be determined in both groups following a biopsy (tumor tissue sample). A second biopsy will then be performed to re-determine the Ki-67 index. The study is open-label, meaning that both the medical staff and the patient know which medications are being administered. The treatments and follow-up examinations as part of the study will take place over a period of up to 14 weeks, during which the effectiveness of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factor is whether the treatment was able to reduce the tumor’s cell growth (Ki-67 index).

Women aged 18 and older with untreated, hormone receptor-positive, HER2-negative, lobular breast cancer are eligible to participate in this study. The disease must be associated with an increased risk of recurrence (stages 2A–3).