(UroToday.com) The 2026 American Urologic Association (AUA) Annual Meeting was host to an invasive bladder cancer poster session. Dr. Michael Jalfon presented the results of a study evaluating the effects of prior checkpoint inhibitor (CPI) exposure on disease control rates with enfortumab vedotin + pembrolizumab (EV+P) in the 1st line metastatic bladder cancer setting.
The combination of EV+P has rapidly become the preferred first-line treatment for patients with advanced and metastatic urothelial carcinoma following the positive results of EV-302.1 However, as adjuvant immunotherapy becomes increasingly used in high-risk muscle-invasive urothelial carcinoma, an important and clinically relevant question is whether prior exposure to immune checkpoint inhibition—most commonly adjuvant nivolumab—may attenuate the efficacy of subsequent pembrolizumab-containing regimens in the metastatic setting.
To address this question, the investigators performed a retrospective chart review of patients with metastatic urothelial carcinoma treated with first-line EV+P at their institution. Baseline demographic and clinical characteristics were collected, including prior therapies, prior cystectomy, and exposure to checkpoint inhibitors. The outcomes of interest included response rate at the initial three-month restaging scan, treatment failure-free survival, and overall survival (OS), all measured from initiation of EV+P.
A total of 86 patients were included, of whom 73 were checkpoint inhibitor-naïve, and 13 had prior CPI exposure. In the overall cohort, 49% of patients demonstrated an objective response at the first three-month scan, while 51% did not respond.
Notably, there was a marked difference in early response rates when stratified by prior immunotherapy exposure. Among CPI-naïve patients, 53% achieved a response at the initial scan, compared with only 23% of those previously exposed to checkpoint inhibitors (p=0.044). These data suggest that prior PD-1/PD-L1 therapy may substantially diminish the likelihood of achieving an early response to EV+P.
Among patients who responded to treatment, treatment failure-free survival was significantly shorter in those with prior CPI exposure. Median treatment failure-free survival was 178 days in CPI-naïve responders compared with 104 days in responders with prior checkpoint inhibitor exposure, corresponding to a hazard ratio of 2.46 (95% CI 1.06–5.71). This indicates more than a two-fold higher risk of treatment failure despite an initial response.
Overall survival did not differ significantly between groups. At five years, the hazard ratio for OS was 3.13 (95% CI 0.61–16.19), although the wide confidence interval reflects the limited sample size and small number of previously exposed patients.
The investigators concluded that prior checkpoint inhibitor exposure may adversely affect the efficacy of first-line EV+P in metastatic urothelial carcinoma. Specifically, previously treated patients demonstrated lower response rates and shorter treatment-failure free survival compared with checkpoint inhibitor-naïve patients.
These findings are highly relevant in the contemporary treatment landscape, where adjuvant nivolumab is increasingly used after radical cystectomy for high-risk urothelial carcinoma. If validated in larger multi-institutional cohorts, these results may help guide treatment selection and sequencing for patients who develop metastatic recurrence after prior immunotherapy exposure.
Presented by: Michael Jalfon, MD, Resident Physician, Department of Urology, Yale School of Medicine, New Haven, CT
Written by: Rashid K. Sayyid, MD, MSc, Assistant Professor, Urologic Oncologist, Department of Urology at The University of Arizona and Banner University Medical Center, Tucson, AZ – @rksayyid on X during the American Urological Association (AUA) 2026 Annual Meeting, Washington, DC, Fri, May 15 – Mon, May 18, 2026.
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