Evangelia Vlachou, MD, is a postdoctoral research fellow in the Departments of Medical Oncology and Urology at Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins.

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

"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.

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Evangelia Vlachou, MD, discusses the investigation of enfortumab vedotin plus pembrolizumab as perioperative therapy in upper tract urothelial cancer.

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“These numbers show us that we need to further assess the efficacy of enfortumab vedotin and enfortumab vedotin/pembrolizumab in the perioperative setting [through] larger, prospective studies.”

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

This study evaluated response rates and disease control rates (DCRs) in patients with high-grade, locally advanced or metastatic upper tract urothelial cancer and intact primary tumors who were treated with enfortumab vedotin alone or in combination with pembrolizumab. Between December 2017 and June 2024, investigators identified 22 patients with intact primary tumors. Patients had a median age of 72 years, 59.1% of patients were male, 77.3% of patients were White, and 86.4% of patients had pure urothelial cancer histology. In total, 59.1% of patients received enfortumab vedotin monotherapy, and 40.9% of patients received the antibody-drug conjugate in combination with pembrolizumab. Patients received a median of 4 cycles (range, 0.5-14) of enfortumab vedotin. The median duration of treatment was 3.3 months (range, 0.5-10).

Response rates were evaluated by 2 radiologists using RECIST 1.1 criteria among patients with or without target or measurable lesions at baseline scans. The overall response rate was 35.0%, with best responses including partial response (PR; 35.0%), stable disease (SD; 35.0%), and progressive disease (PD; 30.0%). The DCR was 70.0%. Two patients had only non-target lesions at baseline; neither of these patients achieved a complete response (CR) or PD with therapy.

The primary lesion response rate was 25.0%, with best responses including PR (25.0%), SD (45.5%), and PD (12.5%). The DCR was 87.5%. Six patients had only non-target primary tumor lesions at baseline; none of these patients experienced a CR or PD with therapy.

These findings demonstrate the importance of continuing to evaluate the efficacy of enfortumab vedotin with or without pembrolizumab in the perioperative setting through large, prospective clinical trials, Vlachou concludes.

Evangelia Vlachou, MD, discusses response rates with enfortumab vedotin alone or with pembrolizumab in patients with upper tract urothelial cancer.

Evangelia Vlachou, MD

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

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