Platinum-Free Systemic Therapy in First-Line Metastatic Urothelial Carcinoma: Mirage or Oasis in the Platinum Desert?

Abstract

<i>The Oncology Grand Rounds series is designed to place original reports published in the</i> Journal <i>into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series was to help readers better understand how to apply the results of key studies, including those published in</i> Journal of Clinical Oncology<i>, to patients seen in their own clinical practice.</i>The systemic treatment for metastatic urothelial carcinoma has evolved over the past decade; however, changes in the first-line setting have remained elusive and dependent on platinum-based chemotherapy regimens. Hoimes et al now present an update on the results of cohort A of the EV-103 phase Ib/II trial combining enfortumab vedotin and pembrolizumab in the first-line setting for patients with cisplatin-ineligible metastatic urothelial carcinoma. The efficacy results in this small, phase I cohort demonstrate an impressive response rate with the majority of patients deriving benefit in tumor control. In conjunction with the results from cohort K of EV-103, recently reported at the 2022 ESMO Congress, there is much anticipation regarding this combination as a future standard of care. However, despite this combination not including a traditional cytotoxic chemotherapeutic, it is still associated with potentially life-altering treatment-related toxicity, most notably rash and peripheral neuropathy, along with the risks of immune-related adverse events, which will need to be carefully calibrated for patients.