Observational Study on the Tolerability, Efficacy, and Adverse Effects of Treatment with Trastuzumab Deruxtecan

Breast cancer (mammary carcinoma) develops when cells in the mammary gland grow uncontrollably. In advanced stages, the cancer is often inoperable and can spread to other parts of the body (metastasis). Standard treatment in such cases usually consists of a combination of chemotherapy and targeted therapies. The characteristics of cancer cells can vary from patient to patient. However, tumor cells often express the HER2 receptor on their surface (“HER2-positive”). However, there are also patients whose tumor cells do not express the receptor (“HER2-negative”) or express it only in small amounts (“HER2-low”). Drugs have therefore been developed that can specifically recognize this receptor and thus target the cancer cells. It remains unclear to what extent patients with HER2-low also benefit from therapy targeting this receptor. For HER2-positive patients, there are specific drugs that block the HER2 receptor. Trastuzumab deruxtecan (T-DXd) is what is known as an antibody-drug conjugate: the antibody trastuzumab is linked to a chemotherapeutic agent (deruxtecan). This allows the cancer cells to be specifically targeted and destroyed. The drug has already been approved and is used to treat inoperable, metastatic breast cancer when previous therapy has been unsuccessful.

The goal of the PROVIDENCE study is to observe the actual course of treatment, the drug’s efficacy, side effects, and patients’ experiences with the therapy. The study does not prescribe any specific treatment plans. Diagnosis and treatment frequency are at the discretion of the treating physicians. Participation may also include the use of a digital health application (DiGA) that supports patient management. The study is open-label, meaning that both medical staff and patients know which medications are being taken. Over a period of up to five years, the study collects patient reports on quality of life and evaluates treatment success in clinical practice. For comparison, patients are divided into two groups: HER2-positive and HER2-low. The study is purely observational; no new medications or therapies are being tested.

Women and men who are at least 18 years old and have HER2-positive or HER2-low breast cancer are eligible to participate in the study. The disease must be at an advanced stage (stages 3–4) and must be inoperable or metastatic. In addition, patients should have already received at least one anti-HER2 therapy (for HER2-positive tumors) or prior chemotherapy (for HER2-low tumors). Exclusion criteria include, among others, an allergy to trastuzumab deruxtecan and concurrent participation in another clinical trial.