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 recently published findings of a phase 1b/2 trial.

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 included 45 cisplatin-ineligible patients with advanced urothelial carcinoma. They received first-line treatment with enfortumab vedotin, a first-in-class antibody-drug conjugate, plus pembrolizumab, a checkpoint inhibitor. Treatment consisted of enfortumab vedotin 1.25 mg/kg once daily on days 1 and 8 and pembrolizumab 200 mg (day 1) intravenously once daily in 3-week cycles.

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Enfortumab vedotin plus pembrolizumab was associated with a manageable safety profile and a 93.3% disease control rate, a team led by Jonathan E. Rosenberg, MD, of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center in New York, New York, reported in the Journal of Clinical Oncology. 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, according to the investigators.

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, Dr Rosenberg and colleagues 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