Longer follow-up data from the CheckMate 274 trial support adjuvant nivolumab as a standard of care for patients with high-risk muscle-invasive urothelial carcinoma (MIUC) after radical surgery, investigators reported at the 2022 American Urological Association annual meeting in New Orleans, Louisiana.
The data show that nivolumab continued to maintain a clinically meaningful improvement in disease-free survival (DFS).
CheckMate 274 included 709 patients with high-risk MIUC. Investigators randomly assigned 353 patients to receive nivolumab and 356 to receive placebo for 12 months of adjuvant therapy after radical surgery. The first analysis of trial results showed that nivolumab was significantly associated with a 30% decreased risk for disease recurrence compared with placebo in the intent-to-treat (ITT) arm and 45% decreased risk among patients with tumor PD-L1 expression ≥1%.
For the latest analysis, Matthew Galsky, MD, from the Icahn School of Medicine at Mount Sinai, New York, New York, and colleagues looked at results after an additional 5 months of follow-up. With the longer follow-up, the ITT group had a minimum of 11 months of follow-up, with a median follow-up of 24.4 months in the nivolumab group and 22.5 months in the placebo group. The PD-L1≥1% group had a minimum follow-up of 11.4 months, with median follow-ups of 25.5 and 22.4 months in the nivolumab and placebo groups, respectively.
In the ITT group, median DFS was 22.0 months in the nivolumab group compared with 10.9 months in the placebo arm. In the PD-L1 ≥1% group, median DFS was not reached in the nivolumab group and 8.4 months in the placebo arm. Compared with placebo recipients, nivolumab-treated patients in the ITT and PD-L1 ≥1% groups had a significant 30% and 47% decreased risk for disease recurrence, respectively. The DFS probability at 12 months was 63.5% in the nivolumab group compared with 46.9% in the placebo arm. In the patients with PD-L1 expression ≥1%, the DFS probability at 12 months was 67.6% with nivolumab and 46.3% with placebo.
“The findings are clinically relevant as they reinforce the earlier results from this trial, which ultimately led to the integration of adjuvant nivolumab into standard care,” Dr Galsky said.
Improvements in DFS were found with nivolumab versus placebo for most subgroups analyzed (including age, sex, ECOG performance status, nodal status, use of prior cisplatin-based chemotherapy, and PD-L1 status). In both study arms, the investigators also observed improvement in non–urothelial tract recurrence-free survival and distant metastasis-free survival with nivolumab vs placebo.
Although the findings are not unexpected, a question remains as to whether improved DFS will translate into an overall survival benefit, according to Lewis Thomas, MD, assistant professor of surgery at Washington University School of Medicine in St. Louis, Missouri. “I think most of us believe it will, as progressive urothelial cancer tends to be a lethal entity, but it will be nice to see that data in the coming years,” Dr Thomas said.
As with all adjuvant therapies, there is a considerable risk of overtreatment, he noted. “So, further research will be invaluable to sort out the best candidates for this therapy,” he said. “I believe the group has some pending biological correlates being analyzed.”
Galsky M, Witjes JA, Gschwend JE, et al. Disease-free survival with longer follow-up from the CheckMate 274 trial of adjuvant nivolumab in patients after surgery for high-risk muscle-invasive urothelial carcinoma. Presented at: AUA2022, May 13-16, 2022, New Orleans, Louisiana. Abstract PD10-01.