Reduced BCG vaccine instillation schedule unsuitable for NMIBC
medwireNews: Reducing the frequency of Bacillus Calmette-Guérin (BCG) vaccine instillations during induction and maintenance treatment for non-muscle-invasive bladder cancer (NMIBC) results in earlier disease recurrence relative to a standard instillation schedule, NIMBUS study data show.
On the basis of these findings, recruitment to the phase 3 trial was stopped and individuals still undergoing treatment with the reduced schedule were given the opportunity to switch to the standard schedule, Marc-Oliver Grimm (Jena University Hospital, Germany) told delegates at the 2020 Genitourinary Cancers Symposium in San Francisco, California, USA.
Grimm explained that NIMBUS set out to investigate whether a reduced frequency of BCG instillations during induction and maintenance would result in noninferior clinical efficacy to a standard frequency, with potentially fewer adverse events, as well as reduced inconvenience and cost. A reduced frequency would also be useful given the BCG shortage, he said.
At the time of the current analysis, after a median 12 months of follow-up, 175 BCG-naïve patients with high-grade Ta-T1 NMIBC with or without concomitant carcinoma in situ had been randomly assigned to receive a standard BCG vaccine dose with a schedule of once-weekly instillations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months, for a total of 15 instillations.
For the reduced schedule, 170 patients were assigned to receive weekly BCG instillations on weeks 1, 2, and 6 during induction and then on weeks 1 and 3 at months 3, 6, and 12 for maintenance, giving nine instillations overall.
Grimm reported that, at 12 months, the recurrence rate was 11% in the standard frequency arm and 24% in the reduced frequency arm. At 24 months the rates were 15% and 34%, respectively.
He also noted that the recurrence curves “separate very early,” with an absolute difference of 10% between the two groups already apparent by 6 months.
At a median of 12 months of follow-up, the hazard ratio for recurrence was a significant 0.40 in favor of the standard schedule. Moreover, the lower boundary of the 97.5% confidence interval was 0.24, which was considerably lower than the limit of 0.75 set to indicate noninferiority.
“So, the experimental arm is clearly inferior,” Grimm remarked.
Nonetheless, in line with the original hypothesis, the study showed that reducing the frequency of treatment resulted in fewer adverse events, with rates of 82.4% and 68.5% reported in the standard and reduced arms, respectively.
Grimm concluded that, “in high-grade non-muscle invasive bladder cancer, a reduced frequency of BCG instillations during induction and maintenance is inferior to the standard BCG schedule regarding time to first recurrence.”
He added: “The study will end in April of this year with a little bit longer follow-up to provide more mature data on the patients who have already been treated.”
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