Adjuvant nivolumab after radical surgery significantly improves disease-free survival (DFS) in patients with high-risk muscle-invasive urothelial carcinoma (MIUC), according to research published in The New England Journal of Medicine.
The phase 3 CheckMate 274 trial (ClinicalTrials.gov Identifier: NCT02632409) enrolled 709 patients with MIUC who had undergone radical surgery with or without neoadjuvant cisplatin-based chemotherapy.
The patients were randomly assigned 1:1 to receive adjuvant nivolumab (n=353) or placebo (n=356) every 2 weeks for up to 1 year. Patients were stratified based on PD-L1 expression, pathologic nodal status, and whether or not they had received neoadjuvant cisplatin-based chemotherapy.
The median follow-up was 20.9 months for patients treated with nivolumab and 19.5 months for patients treated with placebo.
In the intention-to-treat population, the median DFS was 20.8 months in the nivolumab arm and 10.8 months in the placebo arm. The 6-month DFS rate was 74.9% in the nivolumab arm and 60.3% in the placebo arm (hazard ratio [HR], 0.70; 98.22% CI, 0.55-0.90; P <.001).
Among patients with a PD-L1 expression level of 1% or higher, the 6-month DFS rate was 74.5% in the nivolumab arm and 55.7% in the placebo arm (HR, 0.55; 98.72% CI, 0.35-0.85; P <.001).
The median survival free from recurrence outside the urothelial tract was 22.9 months in the nivolumab arm and 13.7 months in the placebo arm. The percentage of patients who were free from recurrence outside the urothelial tract at 6 months was 77.0% in the nivolumab arm and 62.7% in the placebo arm (HR, 0.72; 95% CI, 0.59-0.89).
Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 17.9% of patients treated with nivolumab and 7.2% of patients treated with placebo.
The most common grade 3 or higher TRAEs associated with nivolumab were elevation in serum levels of lipase (5.1%) and amylase (3.7%), diarrhea (0.9%), colitis (0.9%), and pneumonitis (0.9%).
There were 2 treatment-related fatalities due to pneumonitis in the nivolumab arm.
“The CheckMate 274 trial showed a significant and clinically meaningful benefit of adjuvant systemic immunotherapy as compared with placebo, both in the intention-to-treat population and in patients with a PD-L1 expression level of 1% or more,” the study authors wrote.
Disclosures: This research was supported by Bristol Myers Squibb and Ono Pharmaceutical. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384(22):2102-2124. doi:10.1056/NEJMoa2034442