The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These resultsat the virtual annual congress of the European Association of Urology.
More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.
At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.
“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator, of Jena (Germany) University Hospital.
“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.
Dr. Grimm presented the recently published findings from NIMBUS () alongside some new information from a post hoc analysis.
was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.
The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation,.
Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial,, of the University of British Columbia in Vancouver.
Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.
“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.
Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.
“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.