A study assessed the feasibility, toxicity, and activity of durvalumab plus tremelimumab with concurrent radiotherapy (RT) in patients with localized muscle invasive bladder cancer (MIBC). The results of the phase II IMMUNOPRESERVE-SOGUG trial were presented during the 2021 ASCO Annual Meeting.
“Bladder-preserving combined modality therapies constitute an alternative to radical cystectomy for selected patients with MIBC. In preclinical studies, combination of radiation and dual checkpoint blockade appears to activate non-redundant immune mechanisms, potentiating antitumor activity,” the researchers explained.
They evaluated patients with localized MIBC in clinical stages T2-4a who had no contraindications to immunotherapy who either wanted bladder preservation or could not undergo cystectomy. Patients received initial transurethral resection (TUR) of the tumor, followed by durvalumab 1,500 mg intravenously (IV) plus tremelimumab 75 mg IV, every four weeks for three doses. Two weeks later, they began normofractionated external-beam RT (46 Gy to minor pelvis, 64-66 Gy to bladder). The primary endpoint was complete response (CR).
Final analysis included 32 patients at six centers with a median age of 71 years who underwent at least two immunotherapy cycles. At post-treatment biopsy, 26 patients attained CR, two patients had residual MIBC, and four patients were not evaluated due to rejection, clinical impairment, death from COVID-19, and a suspected treatment-related death from peritonitis (n=1 for all).
Median follow-up was 6.1 months, at which time two patients required salvage cystectomy. The estimated six-month disease-free survival (DFS) rate with bladder intact was 76%, DFS was 80%, and overall survival was 93%. The most common adverse events (AEs) related to RT and/or immunotherapy were diarrhea (41%) and urinary disorders (37.5%). Overall, 31% of patients experienced grade 3 or 4 AEs, the most common of which were gastrointestinal toxicity (12.5%), acute kidney failure (6%) and hepatitis (6%).