William P. Skelton IV, MD
Assistant Professor, Department of GU Oncology
In this edition of Grand Rounds in Hematology and Oncology from April 2024, Daniel Reed, MD, Hematologist, University of Virginia, Charlottesville, Virginia, introduces William P. Skelton IV, MD, Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, Virginia. In this 58-minute presentation, Dr. Skelton presents an in-depth update on the evolving management of metastatic urothelial carcinoma, highlighting key data shaping current practice and future directions. The talk includes a short Q&A discussion at the end.
Dr. Skelton outlines the integration of antibody-drug conjugates (ADCs) into treatment algorithms, particularly the role of enfortumab vedotin (EV) in combination with pembrolizumab, which has demonstrated efficacy in the first-line setting. This is supported by the EV-302 trial, which showed this combination significantly improves overall survival and progression-free survival compared to standard platinum-based chemotherapy, establishing it as a new standard of care. He contrasts this with the CheckMate 901 trial, which assessed nivolumab plus gemcitabine-cisplatin. While that combination improved overall survival compared to chemotherapy alone, its impact is less robust than the EV/pembrolizumab regimen. Dr. Skelton stresses the importance of sequencing and patient selection in optimizing outcomes, noting that while FGFR inhibitors such as erdafitinib are approved for select patients with FGFR alterations, their use may diminish as EV-based combinations move earlier in treatment.
Skelton also discusses the role of maintenance avelumab following chemotherapy; however, he acknowledges that access and toxicity profiles will influence real-world adoption. Toxicities such as rash, neuropathy, and hyperglycemia with EV require proactive management, and careful attention to performance status and comorbidities is essential when choosing regimens.
Looking ahead, Dr. Skelton points to emerging trials exploring combinations of ADCs with checkpoint inhibitors and FGFR inhibitors, aiming to refine sequencing strategies. He emphasizes the need for biomarkers to personalize therapy and ensure long-term benefits. The evolving landscape calls for a multidisciplinary, patient-centered approach as treatment options expand.