New drug or new combination of drugs for triple-negative breast cancer and detectable residual disease following neoadjuvant therapy

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue characterized by the 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), the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased expression of the HER2 receptor on the cells (HER2-positive). If none of these receptors are present, the cancer is referred to as triple-negative breast cancer. The stage of the disease is also very important: While in the locally confined stage (stages 1–2) the disease is limited to the breast, the locally advanced stage (stage 3) means that the tumor is already larger or that lymph nodes are involved. Treatment for stage 1–3 triple-negative breast cancer typically involves preoperative drug therapy (neoadjuvant therapy) and surgical removal of the tumor. If cancer cells are still detectable after this procedure, follow-up drug treatment (adjuvant therapy) is generally recommended. Among the options available are the already approved drugs capecitabine and pembrolizumab, which are designed to stop tumor growth. The new, not-yet-approved drug datopotamab deruxtecan (Dato-DXd) could represent a new treatment option in this context. Dato-DXd is an antibody-drug conjugate that binds to a receptor on the surface of cancer cells and releases the cell-damaging active ingredient inside the cancer cells. This drug can also be administered in combination with the antibody durvalumab. Durvalumab is already approved for the treatment of other forms of cancer.

The goal of this Phase 3 study is to investigate the efficacy and safety of Dato-DXd + durvalumab compared to monotherapy with Dato-DXd and standard adjuvant therapy with capecitabine or pembrolizumab. Patients will be randomly assigned to one of three groups as part of the study. Group 1 will receive the combination therapy Dato-DXd plus durvalumab, Group 2 will receive Dato-DXd as monotherapy, and Group 3 will receive standard adjuvant therapy with capecitabine or pembrolizumab (the exact regimen will be selected by the treating physicians). The study is open-label, meaning that both the medical staff and the patients 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 five years, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. The primary endpoint of the study is disease-free survival.

Women and men aged 18 and older with triple-negative breast cancer (stages 1–3) and detectable residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy and surgical removal of the tumor are eligible to participate in the study.