Dr Narayan on the Evolving Treatment Paradigm in Metastatic Urothelial Carcinoma

Vivek K. Narayan, MD, MS, assistant professor, medicine (hematology-oncology), the Hospital of the University of Pennsylvania, physician, Penn Medicine, discusses potential avenues for treatment considerations in patients with metastatic urothelial carcinoma.

The number of treatment options for patients with metastatic urothelial cancer is likely to increase with the advent of further research, specifically for those with previously untreated disease, Narayan says. In 2021, the FDA approved single-agent enfortumab vedotin-ejfv (Padcev) in the treatment of patients with locally advanced or metastatic urothelial cancer who have previously received treatment with platinum-based chemotherapy and a PD-(L)1 inhibitor or those who have previously received at least 1 prior line of therapy and are ineligible for cisplatin-containing chemotherapy. This regulatory decision was supported by findings from the phase 3 EV-301 trial (NCT03474107), in which the antibody-drug conjugate elicited an overall response rate (ORR) of 40.6% (95% CI, 34.9%-46.5%) vs 17.9% (95% CI, 13.7%-22.8%) with investigator’s choice of single-agent chemotherapy (P < 0.0001).

The combination of enfortumab vedotin and pembrolizumab (Keytruda) was approved by the FDA on April 3, 2023, for cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer. This regulatory decision was based on data from the combined dose-escalation/cohort A and cohort K of the phase 1/2 EV-103/KEYNOTE-869 study (NCT03288545), in which the regimen generated a confirmed ORR of 68% (95% CI, 59%-76%), including a complete response rate of 12% and a partial response rate of 55%.

Additionally, findings from the phase 3 CheckMate-901 trial (NCT03036098) demonstrated that treatment with nivolumab (Opdivo) plus cisplatin-based chemotherapy followed by nivolumab monotherapy led to a 22% reduction in the risk of death compared with standard-of-care cisplatin-based chemotherapy in patients with treatment-naïve, unresectable or metastatic urothelial carcinoma (HR, 0.78; 95% CI, 0.63-0.96; P = .0171).

The variety of treatment regimens for metastatic urothelial cancer can elicit different benefits for patients, along with different toxicity profiles, leading to questions regarding optimal frontline therapies, Narayan explains. Treatment decisions for patients in this population will become more complex than determining which patients are cisplatin-eligible and –ineligible, Narayan concludes.