Efficacy thresholds for the regulatory approval of novel therapies in bladder cancer

What is it about?

We simulated the clinical course of billions of bladder cancer patients on the Niagara supercomputer and found out that efficacy thresholds for the regulatory approval of novel therapies in BCG-unresponsive non-muscle invasive bladder cancer are probably too low.

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Why is it important?

BCG-unresponsive non-muscle invasive bladder cancer is a highly aggressive and dangerous disease. Surgical removal of the bladder (radical cystectomy) is the standard therapy but comes at a high mortality and morbidity. Therefore, patients are often unfit or not willing to undergo this procedure. As a result, novel therapies that can spare the bladder are desperately warranted. Randomized controlled trials, usually used to compare a new treatment A to an established treatment B, are currently not practical to investigate the efficacy of such novel therapies since a trial with radical cystectomy as control therapy would be an unfeasible control while a trial with a placebo control would be considered unethical. Thus well-conducted single-arm trials are needed to inform which novel therapies should be accepted. To guide the design of such single‐arm trials, expert groups published recommendations for clinically meaningful outcomes. Our simulation demonstrated that the current recommendations regarding clinically meaningful outcomes for single‐arm trials evaluating the efficacy of novel therapies in BCG‐unresponsive non-muscle invasive bladder cancer may be too low. Based on our quantitative approach, we propose increasing the thresholds to promote the development of clinically truly meaningful novel therapies. Our results are particularly interesting in the light of the recent FDA approval of pembrolizumab (January 2020).

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