(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 13th and 15th 2025, was host to the Poster Session B: Urothelial Carcinoma. Dr. Tanya Jindal presented Abstract 867: Outcomes of enfortumab vedotin and pembrolizumab for patients previously treated with immune checkpoint inhibitors in the UNITE study.
The first-line combination therapy of enfortumab vedotin and pembrolizumab has shown superior outcomes compared to platinum-based chemotherapy in the EV-302 trial, establishing it as the standard of care for metastatic urothelial carcinoma.1 However, prior treatment with immune checkpoint inhibitors (ICIs) was not allowed in clinical trials evaluating this combination in metastatic urothelial cancer.
An important unanswered question is whether rechallenging patients with enfortumab vedotin plus pembrolizumab after prior ICI exposure remains effective. The authors hypothesized that enfortumab vedotin (EV) plus pembrolizumab would remain effective in patients with prior ICI exposure, and this study aimed to evaluate that hypothesis.
Dr. Jindal and colleagues analyzed data from the retrospective multisite cohort study UNITE, a collaboration among multiple academic centers across the United States. For this study, patients who had received prior ICIs before starting EV plus pembrolizumab were identified and included.
The investigators evaluated several variables to assess their potential impact on outcomes with EV plus pembrolizumab, including:
- Type of ICI received (PD-1 vs. PD-L1)
- Prior pembrolizumab vs. other ICI
- Time from last ICI to initiation of EV + pembrolizumab
- Duration of prior ICI treatment
- Clinical benefit from prior ICI
- Whether ICI was the immediate prior therapy and whether it was the only prior line of treatment
The time-to-event endpoints of this analysis included:
- Progression-free survival (PFS)
- Overall survival (OS)
The objective response rate (ORR) was assessed and compared in patients who had undergone imaging after at least one cycle of EV plus pembrolizumab using logistic regression.
The investigators found that among 220 patients treated with EV plus pembrolizumab across 14 U.S. sites, 43 (20%) had previously received ICIs. Of these, 9% had received ICIs in the perioperative setting, while 91% had received them in the metastatic setting. The median age was 69 years, with the majority of patients being Caucasian. The primary tumor location was in the lower tract for 65% of patients and the upper tract for 35%. Sixty-three percent of patients had pure urothelial histology, and only 4% had pure variant histology. Baseline and demographic characteristics are presented below.
The median follow-up for this cohort was 14 months, with a median overall survival (OS) of 15.4 months, a median progression-free survival of 6.9 months, an objective response rate (ORR) of 54%, and a disease control rate of 79%.
Notably, 9% of patients achieved a complete response, 40% had a partial response, and 30% experienced stable disease while being treated with EV and pembrolizumab, despite prior ICI exposure.
Regarding treatment and survival outcomes by pre-specified groups, there was a marginally significant association between time on prior ICI and ORR (OR 0.87 [95% CI 0.74–0.98]; p=0.05) and between prior pembrolizumab use and OS (HR 0.40 [95% CI 0.15–1.02]; p=0.05).![Regarding treatment and survival outcomes by pre-specified groups, there was a marginally significant association between time on prior ICI and ORR (OR 0.87 [95% CI 0.74–0.98]; p=0.05) and between prior pembrolizumab use and OS (HR 0.40 [95% CI 0.15–1.02]; p=0.05).](/images/com-doc-importer/190-asco-gu-2025/asco-gu-2025-outcomes-of-enfortumab-vedotin-and-pembrolizumab-for-patients-previously-treated-with-immune-checkpoint-inhibitors-in-the-unite-study/image-3.jpg)
Dr. Jindal wrapped up her poster presentation with the following conclusions:
- Patients treated with EV plus pembrolizumab following prior treatment with an immune checkpoint inhibitor demonstrated robust ORR, disease control rates and survival rates.
- Findings from this multi-site retrospective UNITE study are hypothesis-generating and warrant prospective validation in larger cohorts.
Presented by: Tanya Jindal, Senior Clinical Research Coordinator, HDF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
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