Post hoc analysis
Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.
The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).
However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).
Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.
Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.
“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.
“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”
“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.
The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.
SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/