Observational Study of Nerve Damage (Peripheral Neuropathy) During Initial Treatment with Enfortumab Vedotin and Pembrolizumab in Patients with Advanced or Metastatic Urothelial Carcinoma

Urothelial carcinoma originates in the cells of the urothelium, a specialized layer of mucous membrane (epithelial tissue) that lines the interior of the urinary tract (renal pelvis, ureter, bladder, and urethra). Bladder cancer is the most common type of urothelial carcinoma. A urothelial carcinoma is considered locally advanced if it has grown beyond its organ of origin into surrounding tissue or adjacent organs. At this stage, the cancer often cannot be completely removed surgically (inoperable). If the cancer has spread to distant lymph nodes or other organs and formed secondary tumors (metastases) there, it is referred to as a metastatic tumor. At this stage, the disease is typically treated with systemic therapy. This includes immunotherapies, targeted therapies, and platinum-based chemotherapy. Enfortumab vedotin is an antibody-drug conjugate. Its antibody component binds to a protein that is present in increased amounts on the surface of cancer cells. After binding, it is taken up into the tumor cell, where the conjugated active ingredient, monomethyl auristatin E (MMAE), is released. MMAE disrupts the cell’s structural framework (microtubules), thereby blocking cell division. This causes the cancer cells to die. Peripheral neuropathy refers to nerve damage that occurs outside the brain and spinal cord. Peripheral neuropathy is one of the common side effects of enfortumab vedotin. It typically first manifests in the feet and later in the hands as abnormal sensations and sensory disturbances such as numbness, tingling, or pain. Pembrolizumab is an antibody belonging to the class of immune checkpoint inhibitors. It blocks the PD-1 checkpoint on activated immune cells (T cells), thereby enabling the body’s own immune system to once again recognize and fight cancer cells. Both active ingredients are typically administered as an intravenous infusion. The occurrence of nerve damage is assessed before the start of treatment (baseline), at weeks 18, 36, and 52, and after the end of therapy using a questionnaire.

The goal of this observational study is to more accurately assess peripheral neuropathy as a side effect of this first-line treatment in routine clinical practice. The study will examine how frequently it occurs, how severe it is, how it affects quality of life, and whether treatment needs to be adjusted as a result. This is a prospective, non-interventional observational study. Treatment is therefore not dictated by the study but is administered as in standard clinical practice. Patient data will be collected continuously throughout the course of their treatment.

Eligible participants are patients aged 18 years or older with histologically confirmed metastatic or locally advanced, inoperable urothelial carcinoma. Patients must not have received any prior systemic therapy for this condition. In addition, treatment with enfortumab vedotin and pembrolizumab must be feasible. Patients who are contraindicated for either drug, who have already received similar active substances, or who have received platinum-based chemotherapy within the last twelve months are ineligible to participate.