(UroToday.com) The 2025 EAU annual meeting featured a game changer session and a presentation by Dr. Sarah Psutka discussing perioperative outcomes of neoadjuvant TAR-200 + cetrelimab or cetrelimab alone in patients with muscle invasive bladder cancer ineligible for or refusing neoadjuvant cisplatin-based chemotherapy. Standard of care for muscle invasive bladder cancer (T2 – T4 N0M0) includes radical cystectomy with cisplatin based neoadjuvant chemotherapy, which has demonstrated a 23% increase in survival benefit versus radical cystectomy alone. However, up to 50% of patients with muscle invasive bladder cancer are ineligible for such neoadjuvant treatment, and patients receiving cisplatin based neoadjuvant chemotherapy can experience a decrease in general health status and lean muscle mass, increased asthenia and gastrointestinal events, and a delay in time to radical cystectomy. Additionally, perioperative mortality 30- and 90-days post radical cystectomy is observed in 2-3% and 3-8% of patients, respectively. Thus, there is a high unmet need for effective neoadjuvant treatments for patients with muscle invasive bladder cancer who are cisplatin ineligible or cisplatin refusing that maintain overall health status and does not delay or increase complications of planned radical cystectomy.
Patients eligible for SunRISe-4 were randomized 5:3 to four cycles of TAR-200 + cetrelimab (cohort 1) or four cycles of cetrelimab monotherapy (cohort 2). The primary endpoint was pathological complete response rate (ypT0N0), and key secondary endpoints included recurrence free survival and safety:
TAR-200 is a novel intravesical drug releasing system designed to provide sustained delivery of gemcitabine in the bladder. Previously presented at ESMO 2024, in an interim analysis of SunRISe-4, neoadjuvant TAR-200 + cetrelimab showed a higher pathological complete response rate of 42% and overall response rate of 62% compared to cetrelimab monotherapy (23% and 36%, respectively). The most frequent treatment related adverse events in either cohort were grade 1-2 urinary events. At EAU 2025, Dr. Psutka presented the perioperative outcomes of TAR-200 + cetrelimab treatment combination.
The main objective of this analysis was to determine pre- and post-radical cystectomy surgical, laboratory, and safety outcomes with TAR-200 + cetrelimab and cetrelimab monotherapy. Of note, the protocol-specified radical cystectomy window was 11 to 15 weeks after neoadjuvant therapy. At the data cut off of May 31, 2024, 76 patients had undergone radical cystectomy, 50 in cohort 1 and 26 in cohort 2.
Demographics and baseline disease characteristics were balanced across treatment cohorts:
Surgical approaches were per the physician's preference, with robotic cystectomy more commonly performed in cohort 1 (64.0%), and open radical cystectomy more commonly performed in cohort 2 (57.5%). An ileal conduit was the most frequently used type of urinary diversion in either cohort:
ECOG performance status was preserved in the majority of patients in both cohorts, and there were no clinically significant changes in BMI, albumin, creatinine, and hemoglobin during the neoadjuvant period:
Across both cohorts (n = 76), the median time from neoadjuvant initiation to radical cystectomy was 13.5 weeks (range: 4.1-19.4). Importantly, 64 of 76 (84%) patients had a radical cystectomy within the protocol specified window. Among the 8 patients who had a radical cystectomy after the protocol specified window, only one radical cystectomy was delayed because of a treatment related adverse event of hematuria in the cetrelimab monotherapy cohort:
The 30- and 90-day post-radical cystectomy morbidity and mortality were consistent with historical data, and there were no new immune related treatment emergent adverse events reported after radical cystectomy:
Dr. Psutka concluded her presentation by discussing perioperative outcomes of neoadjuvant TAR-200 + cetrelimab or cetrelimab alone in patients with muscle invasive bladder cancer ineligible for or refusing neoadjuvant cisplatin-based chemotherapy with the following take home points:
- In patients with muscle invasive bladder cancer who are cisplatin ineligible or cisplatin refusing, these preliminary results suggest that neoadjuvant TAR-200 + cetrelimab may have the potential to improve oncological outcomes without:
- Decline in overall health status
- Significant increase in postoperative morbidity or mortality
- Delays in planned radical cystectomy
- Further data on pathological complete response and later outcomes, including metastasis and overall survival, are planned
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the European Association of Urology (EAU) 2025 Annual Meeting, Madrid, Spain, Fri, Mar 21 – Mon, Mar 24, 2025.