Metastatic Urothelial Cancer Articles

Metastatic urothelial cancer (mUC) is an aggressive disease with limited overall survival and treatment options. Antibody-drug conjugates (ADCs) were designed with the intent to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells by linking cytotoxins to monoclonal antibodies (mAbs) and have emerged as new treatment options in mUC, mainly in chemotherapy (CT) and immune-checkpoint inhibitors (ICI)-exposed patients.

The therapeutic landscape of metastatic urothelial carcinoma (mUC) becomes increasingly dense: standard therapy remains cisplatin-based chemotherapy, followed by immunotherapy with checkpoint inhibitors as maintenance or second-line.

Enfortumab vedotin (EV) is an antibody-drug conjugate approved for the treatment of refractory advanced urothelial cancer. Cutaneous toxicity is well described but has not been correlated with response.

The Javelin Bladder 100 trial was the first trial to establish the role of switch maintenance therapy in patients with metastatic urothelial cancer using avelumab, a PD-L1 inhibitor, for patients who achieve complete response, partial response, or stable disease to standard chemotherapy of 4-6 cycles with gemcitabine and cisplatin or carboplatin.

The value of programmed cell death ligand-1 (PD-L1) to predict durable responses to immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma (mUC) is inconsistent. We hypothesize that the use of archived primary tumor material (PRIM) for PD-L1 testing in clinical trials not properly reflecting the metastatic disease status (MET) contributes to this clinical issue.

The IO Score is a 27-gene immuno-oncology (IO) classifier that has previously predicted benefit to immune checkpoint inhibitor (ICI) therapy in triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC).