Padcev Plus Keytruda Shows Promise for Upper Tract Urothelial Carcinoma Lesions

Padcev plus Keytruda showed promising clinical activity in UTUC lesions, with a 35% ORR in measurable lesions and an 87.5% disease control rate in primary tumors.

Among patients with upper tract urothelial carcinoma (UTUC) lesions, the combination of Padcev (enfortumab vedotin) and Keytruda (pembrolizumab) resulted in promising clinical activity, study results have shown.

Results from a small retrospective analysis were shared in a poster at the 2025 ASCO Genitourinary Cancers Symposium.

The study, conducted by a team of researchers from the Johns Hopkins Departments of Medical Oncology and Urology, showed that in primary lesions for 16 patients treated with Padcev alone or Padcev plus Keytruda, the overall response rate (ORR) was 25% (four patients), consisting of all partial responses. Primary lesions for an additional 10 patients showed stable disease, for a disease control rate of 87.5% (14 patients). Two patients had progressive disease.

Among all patients with measurable target lesions at baseline (20 patients) the ORR was 35% (seven patients), consisting of all partial responses. An additional seven patients had stable disease for a disease control rate of 70% (14 patients). Six patients had progressive disease.

Study Design and Rationale

In describing the rationale for their retrospective study, the authors explained that patients with UTUC are often ineligible for standard perioperative care with cisplatin due to renal dysfunction related to disease and surgery. They added that, “Given the unprecedented activity of [Padcev] plus [Keytruda] [previously demonstrated] in advanced urothelial carcinoma, and safety in impaired renal function, the assessment of this combination in earlier disease settings for patients with UTUC is an urgent need.”

For their analysis, the researchers included patients with intact primary UTUC tumors who had received single-agent Padcev or Padcev plus Keytruda at Johns Hopkins. They collected baseline patient characteristics through chart review. The study parameters defined primary tumor as any lesion located in the ureter and/or renal pelvis.

The researchers identified 50 patients with UTUC treated with Padcev alone or Padcev plus Keytruda at Johns Hopkins between December 2017 and June 2024. Of these patients, 22 had intact primary tumors and were thus included in the retrospective analysis. Baseline characteristics showed that the median patient age was 72 years, 59% (13 patients) were male, and 77.3% (17 patients) were White. Tumor analysis showed that 86.4% of patients (19 patients) had pure urothelial histology and 81.8% of patients (18 patients) had visceral metastases.

Of the 22 patients with intact primary tumors, 59.1% (13 patients) received Padcev alone and 40.9% (nine patients) received Padcev plus Keytruda. Three patients began their Padcev regimen at a reduced dose. The median number of Padcev cycles received was four. The median treatment duration was 3.3 months.

The combination of Padcev and Keytruda is currently approved by the FDA for the treatment of adult patients with locally advanced or metastatic urothelial cancer.

In their conclusion, the researchers wrote, “Larger prospective studies are needed to assess the efficacy of this promising regimen in the perioperative setting for patients with this rare and aggressive disease.”

Reference:

Primary tumor response to enfortumab vedotin with/without pembrolizumab in patients with upper tract urothelial cancer, by Dr. Evangelia Vlachou, et al., Journal of Clinical Oncology.

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