Transcript:Arjun V. Balar, MD: The approval of durvalumab in the second-line setting for metastatic urothelial cancer after progression of platinum-based chemotherapy, adds to the growing armamentarium in bladder cancer treatment. One of the most promising, rewarding aspects of treating patients with a bladder cancer in this current age, is that we have these active and well-tolerated agents that are leading to responses, including complete responses that have been durable. To have an agent like durvalumab available to us adds to our existing armamentarium to offer our patients.

The FDA indication for durvalumab is dosed at 10 mg/kg once every 2 weeks until disease progression or inaccessible toxicity. So, the indication for durvalumab in metastatic urothelial cancer are specifically patients who have progressed after platinum-based chemotherapy, including patients who have progressed within one year, following neoadjuvant platinum-based chemotherapy for muscle-invasive bladder cancer.

Study 1108, or 1108, was a very large phase I trial of durvalumab administered at 10mg/kg every 2 weeks in 15 different solid tumor types. Specifically, on urothelial cancer, they focused on roughly 100 patients who were treated, 94 of whom had previously progressed on platinum-based chemotherapy. What this trial observed was that the overall response rate for patients in this particular study was 20% with advanced urothelial cancer. And then patients who had high levels of PD-L1 expression, this was measured using the SP263 assay on the VENTANA platform and was measured on both tumor cells and infiltrating immune cells. Patients who had either 25% or greater expression on either tumor cells or immune cells had a response rate of 31%. Whereas patients who had neither 25% expression or greater on tumor cells or immune cells had a response rate of 5%, suggesting that this particular biomarker assay can possibly enrich for patients who are most likely to respond. However, still a minority of patients who are PD-L1—negative based on this assay may still respond to therapy.

I have personal experience with durvalumab, in the context of a clinical trial. And in this particular trial, it is testing durvalumab in combination with tremelimumab, which is a CTLA4 antibody, in a variety of solid tumors. My personal experience extends to patients who have advanced bladder cancer, who have progressed on prior platinum-based chemotherapy. So, I have extensive experience with this agent in this particular setting.

Durvalumab appears to be well tolerated and in line with other agents in this class. However, one of the challenges here, in this particular setting, in my experience, is that it has been in combination with another agent. And often CTLA4 antibodies when added to PD-1 or PD-L1 antibodies can have a significant increase in toxicity, which is something that we have observed in other trials testing this combination.

Transcript Edited for Clarity