My Treatment Approach: Navigating First-Line Treatment Options in Locally Advanced and Metastatic Urothelial Cancer

Thomas Powles, MBBS, MRCP, MD, discusses how upon examining an elderly patient experiencing hematuria, they were found to have had a transurethral resection of a bladder tumor, which revealed the presence of muscle-invasive bladder cancer. The patient is determined to have metastatic disease and is ineligible for cisplatin chemotherapy in the first line.

Thomas Powles, MBBS, MRCP, MD, discusses how different trials have been used to study urothelial cancer (UC) treatments, including DANUBE, IMvigor130, and KEYNOTE-361, all of which are frontline, randomized, phase 3 studies that were unsuccessful. A trial that had better results involved nivolumab plus gemcitabine/cisplatin, due to patients being in better physical condition to withstand chemotherapy.

Thomas Powles, MBBS, MRCP, MD, discusses how the KEYNOTE-361 trial failed because of the trial’s design. Data show that the maintenance phase of the trial is what was driving the benefit and that the longest survival with this trial was 17 months with both pembrolizumab and chemotherapy treatment rather than just chemotherapy.

Thomas Powles, MBBS, MRCP, MD, discusses how avelumab maintenance in bladder cancer has been challenging. Specifically in sequenced immune therapy, there was a 25% decrease in patient deaths, but only 50% of the patients survived. Powles also introduces the anatomy of an antibody-drug conjugate (ADC).

Thomas Powles, MBBS, MRCP, MD, discusses how antibody-drug conjugates have demonstrated improvement over chemotherapy. Data from the EV-301 trial shows that the antibody-drug conjugate enfortumab vedotin decreased the risk of death by 30% versus chemotherapy. Later trial data showed that treatment using enfortumab vedotin plus pembrolizumab (EV+P) reduced the risk of patient death by 53%.

Thomas Powles, MBBS, MRCP, MD, discusses how according to the ESMO guidelines, enfortumab vedotin plus pembrolizumab (EV+P) has become the new standard of first-line therapy in advanced urothelial carcinoma, and if there are patients who are ineligible for EV+P, alternatives are available such as nivolumab plus cisplatin/gemcitabine or platinum-based chemotherapy followed by maintenance avelumab.