Dr Vlachou on the Rationale for Evaluating Perioperative Enfortumab Vedotin Plus Pembrolizumab in Upper Tract Urothelial CancerCancer

"Currently, cisplatin-based chemotherapy is the [standard] first-line treatment for the perioperative management of invasive urothelial cancer. [However], patients with upper tract disease are often ineligible to receive cisplatin, not only due to comorbidities but also due to surgery-related renal dysfunction, [resulting in an unmet need]."

Evangelia Vlachou, MD, a postdoctoral research fellow in the Departments of Medical Oncology and Urology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, discusses the rationale for conducting a retrospective study investigating primary tumor responses with enfortumab vedotin-ejfv (Padcev) with or without pembrolizumab (Keytruda) for patients with upper tract urothelial cancer.

Cisplatin-based chemotherapy remains the standard first-line treatment in the perioperative setting for invasive urothelial carcinoma; however, patients with upper tract disease are frequently ineligible for cisplatin due to pre-existing comorbidities and, distinctively, surgery-associated renal dysfunction, Vlachou began. She emphasized that these patients are often underrepresented or excluded from clinical trials, particularly in the preoperative setting.

Given the limited data in this population, Vlachou noted that her team aimed to determine whether enfortumab vedotin, alone or in combination with pembrolizumab—agents that have significantly affected the management of advanced urothelial carcinoma—could demonstrate similar efficacy in the perioperative setting for patients with upper tract involvement. In this study, investigators assessed response and disease control rates (DCRs) in patients with high-grade, locally advanced or metastatic upper tract urothelial carcinoma and intact primary tumors treated with either enfortumab vedotin alone or in combination with pembrolizumab. The overall response rate was 35.0%, including partial response (PR; 35.0%), stable disease (SD; 35.0%), and progressive disease (PD; 30.0%), with a DCR of 70.0%. The primary tumor response rate was 25.0%, with PR, SD, and PD observed in 25.0%, 45.5%, and 12.5% of patients, respectively, Vlachou reported. The DCR for primary lesions was 87.5%.

Vlachou concluded that these preliminary findings suggest the potential utility of enfortumab vedotin, with or without pembrolizumab, in cisplatin-ineligible patients with upper tract disease, particularly those with renal dysfunction who may not be suitable for standard cisplatin therapy.