medwireNews: Results from the phase 3 CheckMate 274 trial support the adjuvant use of nivolumab in patients with muscle-invasive urothelial carcinoma (MIUC) at high risk for recurrence after surgery.
The PD-1 inhibitor achieved significant improvements relative to placebo in the primary endpoints of disease-free survival (DFS) in the intention-to-treat (ITT) and PD-L1-positive populations, presenting author Dean Bajorin (Memorial Sloan Kettering Cancer Center, New York, USA) told delegates of the 2021 Genitourinary Cancers Symposium.
“Nivolumab is the first systemic immunotherapy to demonstrate a statistically significant and clinically meaningful improvement in outcomes when administered as adjuvant therapy” in this patient group, and these findings therefore support the PD-1 inhibitor as a new adjuvant standard of care, he added.
The double-blind study included 709 patients who underwent radical surgery for MIUC in the previous 120 days and had either of the following high-risk characteristics:
- ypT2–ypT4a or ypN+ disease and prior neoadjuvant cisplatin
- pT3–pT4a or pN+ disease, no prior neoadjuvant cisplatin, and ineligible for or declined adjuvant cisplatin
DFS was a median of 21.0 months for the 353 participants who were randomly assigned to receive nivolumab 240 mg every 2 weeks for up to a year. This was significantly longer than the median of 10.9 months achieved by their 356 counterparts who instead received placebo, and equated to a significant 30% reduction in the risk for recurrence or death.
Adjuvant nivolumab led to an even greater risk reduction relative to placebo, at 47%, among the 282 patients with a tumor PD-L1 expression level of at least 1%. The median DFS duration was unreached in the nivolumab group and was 10.8 months in the placebo group.
The DFS benefit afforded by nivolumab was maintained across most subgroups. But differences between patients with bladder primary tumors and those with upper-tract disease, such that the former derived a significant benefit from nivolumab and the latter did not, “are hypothesis generating,” said Bajorin.
The secondary endpoint of non-urothelial tract recurrence-free survival was also significantly better with nivolumab than placebo, at a median of 24.6 versus 13.7 months (hazard ratio [HR]=0.72) in the ITT cohort, and unreached versus 10.9 months (HR=0.54) in the PD-L1-positive cohort.
This was also the case for the exploratory endpoint of distant metastasis-free survival, with the risk for distant recurrence or death reduced with nivolumab versus placebo by a significant 26% and 40% in the ITT and PD-L1-positive populations, respectively.
“The safety and tolerability of nivolumab monotherapy was consistent with prior reports in other tumor types, including those with metastatic urothelial carcinoma,” reported the presenter. Treatment-related adverse events (TRAEs) of at least grade 3 occurred in 17.9% and 7.2% of nivolumab- and placebo-treated, respectively, and led to discontinuation in a corresponding 7.1% and 1.4%.
The most common grade 3 or worse TRAE in the nivolumab versus placebo arm was lipase elevation (5.1 vs 2.6%), followed by amylase elevation (3.7 vs 1.4%) and diarrhea (0.9 vs 0.3%). There were two treatment-related deaths (both due to pneumonitis) in the nivolumab group and none in the placebo group.
Bajorin also reported that health-related quality of life – as assessed by the EORTC-QLQ-C30 global score – did not deteriorate in the nivolumab versus placebo study arms in either the ITT or PD-L1-positive populations.
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2021 Genitourinary Cancers Symposium; 11–13 February