KONGRESSBERICHT

Highlights in Urothelial Carcinoma
At ESMO 2024 in Barcelona, various studies regarding the management of non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC) and locally advanced / metastatic (la/m) bladder cancer were presented. This article aims to give a short overview of one outstanding study of each group.
SunRISe-1 trial Dr. Michiel Van der Heijden presented updated data from the SunRISe-1 trial, which evaluates TAR-200, an intravesical gemcitabine delivery system, and cetrelimab for patients with BCG-unresponsive high-risk NMIBC who are ineligible or decline radical cystectomy. The trial’s Cohorts 1-3 tested TAR-200 with cetrelimab, TAR-200 alone, and cetrelimab alone, respectively. Results show that TAR-200 alone achieved the highest complete response rate at 84%, with a 12-month response rate of 57.4%. Responses were durable, with 82% of patients still in remission after a median follow-up of 9.2 months. The combination therapy (TAR-200 + cetrelimab) resulted in a lower complete response rate (68%) and more frequent severe adverse events (35.8%) than either treatment alone.
NIAGARA trial The results of the awaited NIAGARA trial were presented by Dr. Thomas Powles. This phase 3 trial assessed the efficacy of neoadjuvant durvalumab combined with gemcitabine/cisplatin (GC), followed by radical cystectomy and adjuvant durvalumab, in cisplatin-eligible MIBC patients compared to the current standard of care with neoadjuvant treatment with GC. With 1,063 patients randomized, the trial demonstrated a significant improvement in event-free survival (EFS) and overall survival (OS) for the durvalumab arm. The EFS rate at two years was 67.8% in the durvalumab group, compared to 59.8% in the control arm, with a hazard ratio (HR) of 0.68 (p<0.0001). While the initial pathological complete response (pCR) analysis was not statistically significant, a re-analysis in 2024 confirmed a nominal benefit favoring durvalumab (p=0.0005). At 24 months, OS was 82.2% for patients receiving durvalumab versus 75.2% in the control, with an HR of 0.75 (p=0.016), suggesting a strong survival advantage. Safety profiles between both arms were similar, with manageable adverse events (AEs) and no observed impact on the timing of surgery. These findings support perioperative durvalumab with chemotherapy as a potential new standard for MIBC. Disitamab Vedotin and Pemrbolizumab in the treatment of locally advanced / metastastic urothelial carcinoma Ongoing trials suggest that antibody-drug conjugates could offer targeted therapy for advanced and metastatic urothelial carcinoma. Dr. Matthew Galsky presented phase 2 results for Disitamab Vedotin (DV) combined with Pembroli- zumab (P) in treating HER2-expressing, untreated la/m urothelial carcinoma. Among 20 patients, the combination showed a 75% overall response rate (ORR), with 35% achieving complete and 40% partial responses, effective in both HER2-positive and HER2-low cases (ORR of 66.7% and 78.6%). The DV+P combination was generally well-tolerated, though 45% experienced grade ≥3 adverse events. These promising results support DV+P as a potential therapy for HER2-expressing la/m urothelial carcinoma, with a phase 3 trial (NCT05911295) now recruiting 700 patients, expected to conclude in 2029. Author: MD Silvan Sigg, Luzerner Kantonsspital Mentor: Prof. Dr. Med. Richard Cathomas, Kantonsspital Graubünden References: 1. Van der Heijden M et al.: TAR-200 +/- Cetrelimab and Cetrelimab Alone in Patients With Bacillus Calmette-Guérin–Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer: Updated Results From SunRISe-1. ESMO 2024. 2. Powles T et al.: Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer. N Engl J Med. 2024;391(19):1773-1786. 3. Galsky MD et al.: Preliminary efficacy and safety of disitamab vedotin (DV) with pembrolizumab (P) in treatment (Tx)-naive HER2-expressing, locally advanced or metastatic urothelial carcinoma (la/mUC): RC48G001 cohort C. Ann Oncol. 2024;35(2):S1135-S1169. 24 onkologie  1 | 2025