A new therapeutic approach (drug: datopotamab deruxtecan) for the treatment of triple-negative, untreated breast cancer in neoadjuvant therapy

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue characterized by the uncontrolled proliferation of breast cells. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the stage of the disease, the tumor’s growth rate (Ki-67 index), detectable hormone receptors (HR) 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). If the tumor cells lack all of these receptors, the cancer is referred to as triple-negative breast cancer. Treatment options for triple-negative breast cancer are not yet as extensive as those for hormone receptor- or HER2-positive breast cancer, since many drugs target these specific receptors. Hormone receptor-low, HER2-negative breast cancer presents similar treatment challenges. Treatment is primarily based on chemotherapy, though new targeted drugs are also being used, such as checkpoint inhibitors like pembrolizumab or durvalumab. A new class of drugs acts as highly targeted antibody-drug conjugates: These drugs recognize cancer cells through their antibody component and then deliver a chemotherapy-like active ingredient directly into the cells, causing them to die. A new, as-yet-unapproved drug in this group is datopotamab deruxtecan (Dato-DXd).

A commonly used treatment approach involves a combination of an initial phase of chemotherapy (neoadjuvant), followed by surgery on the breast and, if necessary, the lymph nodes. This is often followed by a further phase of therapy (adjuvant), in which various treatments may be used, including radiation therapy.

The goal of the TROPION-BREAST04 study is to compare the efficacy of two different treatment approaches in patients with triple-negative breast cancer or hormone receptor-low/HER2-negative breast cancer.

To this end, study participants are randomly assigned to two groups, with the assignment known to everyone (open-label). One group receives neoadjuvant datopotamab deruxtecan (Dato-DXd) combined with durvalumab. After surgery, treatment with durvalumab continues, sometimes in combination with an established chemotherapy regimen. The other group receives the antibody pembrolizumab combined with chemotherapy before and after surgery. All medications are administered every three weeks (with the exception of some chemotherapy drugs). The primary objective of the study is to assess the response to therapy at the time of surgery, which takes place after the neoadjuvant therapy phase. Overall, follow-up continues for up to 68 months after the start of the study.

To participate in the study, patients must be at least 18 years old, have untreated stage 2 or 3 triple-negative or hormone receptor-low/HER2-negative breast cancer, and be in good general health (ECOG 0 or 1).