Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago.

In this episode, OncLive On Air® partnered with Two Onc Docs to provide a comprehensive review of metastatic urothelial carcinoma management, contrasting historical standards with the rapidly evolving frontline paradigm. As the field transitions into a new era of care, Drs Armstrong and Tawagi emphasized the importance of understanding trial data and toxicity management for both board preparation and clinical practice.

The discussion began with details about the historical treatment paradigm, which relied on platinum-based chemotherapy followed by maintenance avelumab for patients who did not progress. However, the experts noted that the current SOC has shifted dramatically following findings from the landmark EV-302 trial, which evaluated the combination of enfortumab vedotin and pembrolizumab.

They also explained that the toxicities associated with enfortumab vedotin plus pembrolizumab are highly testable and clinically relevant. Key adverse effects include skin toxicity and peripheral neuropathy, they said. Additionally, the hosts highlighted hyperglycemia and the risk of diabetic ketoacidosis, and emphasized that ocular toxicities, specifically dry eyes, also necessitate referrals to ophthalmology.

In the second-line setting following enfortumab vedotin plus pembrolizumab, Drs Armstrong and Tawagi noted that the paradigm unclear, though treatment options include platinum-based chemotherapy or targeted agents. They recommended testing for FGFR mutations to determine patient eligibility for erdafitinib, as well as testing for HER2 expression to determine eligibility for trastuzumab deruxtecan.

They also reported that for localized high-grade upper tract urothelial carcinoma, treatment options include neoadjuvant split-dose gemcitabine/cisplatin or upfront surgery followed by adjuvant chemotherapy. In the metastatic setting, they noted that rare disease variants like small cell carcinoma are treated with platinum doublets and immunotherapy, whereas adenocarcinoma management may require FOLFOX.