The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) SUBDUE-1 trial, featured in BJU International, published their findings on the safety and immunological implications of sub-urothelial injection of durvalumab in patients with bladder cancer. The study concluded that sub-urothelial injection of durvalumab is both feasible and safe without immune related adverse events and suggests the establishment of a local immunological response.
Bladder cancer features amongst the 10 most prevalent cancers worldwide. At diagnosis, 75% of patients have non-muscle invasive bladder cancer (NMIBC), but these patients experience high rates of disease recurrence and progression to muscle-invasive bladder cancer (MIBC).
Management of NMIBC has hardly changed in three decades and radical cystectomy (RC) is the preferred treatment for patients with BCG unresponsive tumours, but this has a high morbidity and may overtreat patients. This new study wanted to explore whether there were benefits and minimal side effects for NMIBC patients.
A total of 11 patients were recruited (10 male, one female). The study was conducted on patients with non metastatic muscle-invasive bladder cancer who hadn’t received chemotherapy or immunotherapy before. All the patients received sub-urothelial durvalumab at their predetermined dose before undergoing radical cystectomy.
With all the trial participants, there were no significant changes reported on the American Urological Association Symptom Score or O’Leary Interstitial Cystitis Scale and tissue immune populations changed following the durvalumab injection, with a significant increase in M2-macrophage, leading researchers to conclude that durvalumab is feasible and safe without immune-related adverse events and that the procedure showed local immunological benefits.
Study Chair of SUBDUE-1, Professor Dickon Hayne, said about the findings, “I’m really proud of this study and extremely grateful to ANZUP, SMHS, the amazing research team and especially the patients who agreed to participate.
“This study represents the first step in a new approach to checkpoint inhibitor (CPI) therapy in bladder cancer. Whether local administration of CIPs by injection is the preferable approach remains unknown but the potential advantages of less toxicity, greater efficacy and lower cost are self-evident. Further trials with durvalumab and other CPIs are now necessary to further explore this exciting development,” he continued.
Sub-urothelial injections of ICI could prove beneficial for several reasons: a sub-urothelial administration route would facilitate maximal urothelial penetrance; the procedure does not require surgical upskilling; local ICI administration may be safer than systemic delivery with less immune-related adverse effects and it may be effective in BCG-unresponsive bladder cancer.
Durvalumab, a human monoclonal anti-PD-L1 antibody, blocks the PD1/PD-L1 interaction, with systemic administration showing benefit in various cancer types.
Given the success of systemic ICI’s in advanced urothelial cancer, these treatments hold promise in the localised disease with the favourable overall toxicity profile supporting the hypothesis that sub-urothelial durvalumab is safe in bladder cancer.
The trial results suggested that there was no substantive systemic immune activation, however, in contrast, alterations in tissue immune populations across treatment are consistent with the second hypothesis; that this new treatment would exert a local immunological effect.
Source: ANZUP
Paper: Hayne, D., Ong, K., Swarbrick, N., et al. (2024), The SUB-urothelial DUrvalumab InjEction-1 (SUBDUE-1) trial: first-in-human trial in patients with bladder cancer. BJU Int. Access online here.
