The US Food and Drug Administration has approved nivolumab (Opdivo) for the adjuvant treatment of urothelial carcinoma (UC) in cases in which there is a high risk for recurrence following radical resection, according to an announcement from its maker, Bristol-Meyers Squibb (BMS).
The new indication builds on the PD-1 inhibitor’s prior approvals for advanced or metastatic UC that’s progressed during or following platinum-containing chemotherapy or that’s progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
The new indication is based results from the CheckMate -274 trial, which found an almost doubling of median disease-free survival (DFS) with nivolumab compared with placebo.
BMS noted that the new approval makes nivolumab “the first and only PD-1 inhibitor approved for urothelial carcinoma in the adjuvant setting,” regardless of prior neoadjuvant chemotherapy, nodal involvement, or PD-L1 status.
It “has the potential to become a new standard-of-care option in this setting,” said CheckMate-274’s primary investigator, Matthew Galsky, MD, a genitourinary medical oncologist at the Icahn School of Medicine at Mount Sinai, in New York City, in the company press release.
Rival PD-1 blocker pembrolizumab (Keytruda), from Merck, carries several UC indications of its own for locally advanced or metastatic disease in patients who are ineligible for platinum-containing chemotherapy or that has progressed despite it, as well as for high-risk, non–muscle invasive bladder cancer that has not responded to bacillus Calmette-Guérin (BCG) treatment in cases in which patients are ineligible for or opt out of cystectomy, according to labeling.
In the CheckMate-274 trial, 353 patients with UC were randomly assigned to receive nivolumab after radical resection, and 356 others were assigned to receive placebo. Nivolumab was adminstered at 240 mg by intravenous infusion every 2 weeks until recurrence or unacceptable toxicity for a maximum duration of 1 year. Neoadjuvant cisplatin chemotherapy was allowed.
Median DFS was 20.8 months with nivolumab, vs 10.8 months in the placebo arm. Among patients with PD-L1 expression of 1% or more, median DFS was 8.4 months in the placebo group; it was not reached with nivolumab.
Serious adverse reactions occurred in 30% of patients who received nivolumab. The most frequent was urinary tract infection. Fatal reactions, including pneumonitis, occurred in 1%. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, the labeling notes.
The trial was funded by BMS and Ono Pharmaceutical. Galsky has been a paid consultant for BMS.