Enfortumab vedotin plus pembrolizumab may offer a safe and effective alternative therapy for previously untreated advanced urothelial carcinoma in patients who are ineligible to receive cisplatin-based therapies, according to a phase 1b/2 trial published in the Journal of Clinical Oncology.

According to investigators, the median duration of response (DOR) and median overall survival (OS) exceeding 2 years in a cisplatin-ineligible patient population “make this a promising combination.” The treatment is currently being studied in a phase 3 trial.

The phase 1b/2 trial (ClinicalTrials.gov identifier: NCT04223856) included 45 cisplatin-ineligible patients with advanced urothelial carcinoma. They received first-line treatment with enfortumab vedotin at 1.25 mg/kg on days 1 and 8 and pembrolizumab at 200 mg on day 1 of every 3-week cycle.

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Enfortumab vedotin plus pembrolizumab was associated with a manageable safety profile and a 93.3% disease control rate, according to investigators. The investigator-confirmed objective response rate (ORR) was 73.3% (33 patients), with 15.6% (7 patients) achieving a complete response and 57.8% (26 patients) achieving a partial response.

The median DOR was 25.6 months with a median follow-up of 20.0 months. The median OS was 26.1 months with a median follow-up of 24.9 months.

The most common treatment-related adverse event (TRAE) was peripheral sensory neuropathy (55.6%), followed by fatigue (51.1%) and alopecia (48.9%). Of the 45 patients, 29 (64.4%) had grade 3 or higher TRAEs, most commonly increased lipase (17.8%), maculopapular rash (11.1%), and fatigue (11.1%).

Based on their findings, the investigators wrote that “enfortumab vedotin plus pembrolizumab could provide a highly active and durable [first-line] platinum-free option for patients whose disease may not be suitable for treatment with a cisplatin-based chemotherapy, pending prospective validation in randomized studies.”

Citing previous research, the authors noted that approximately half of all patients with locally advanced or metastatic urothelial carcinoma are ineligible for cisplatin chemotherapy because of impaired renal function, poor performance status, and other comorbidities.


Hoimes CJ, Flaig TW, Milosky MI, et al. Enfortumab vedotin plus pembrolizumab in previously untreated advanced urothelial cancer. J Clin Oncol. Published online August 30, 2022. doi:10.1200/JCO.22.01643

This article originally appeared on Renal and Urology News