Adjuvant Nivolumab in Muscle-Invasive Urothelial Carcinoma – Expert Commentary

The role of adjuvant therapy in muscle-invasive urothelial carcinoma is unclear, despite the high risk of metastatic recurrence. Adjuvant cisplatin-based chemotherapy is challenging to administer, and some patients are ineligible for or decline neoadjuvant cisplatin-based chemotherapy. Therefore, ongoing trials are designed to evaluate the efficacy of adjuvant immunotherapy.

A recent study (CheckMate-274) by Bajorin et al. published in The New England Journal of Medicine investigated the efficacy and safety of adjuvant nivolumab versus placebo in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery (with or without previous neoadjuvant cisplatin).

A total of 709 patients was recruited to the trial from 29 international academic centers between 2016 and 2020. They were randomized 1:1 to receive adjuvant nivolumab at 240 mg every two weeks or placebo for up to 1 year. In the nivolumab arm (n=353), 53.3% of patients discontinued treatment versus 56.3% in the placebo arm, commonly due to disease recurrence. No new concerning safety issues were observed from the known safety profile of nivolumab. The median follow-up was up to 21 months.

Investigators found that adjuvant nivolumab resulted in a 30% reduction in the risk of disease recurrence or death in the intent-to-treat population (hazard ratio (HR): 0.70; 98.31% CI, 0.54-0.89; P < .001). In patients with PD-L1 expression level of 1% or more, the reduction of recurrence risk or death was 47% (HR: 0.53; 98.87% CI, 0.34-0.84; P < .001). Numerically, median disease-free survival with nivolumab was longer than placebo (21.0 months versus 10.9 months). The secondary endpoint of non–urothelial tract recurrence-free survival was improved in patients receiving nivolumab compared to placebo (22.9 months versus 13.7 months). The investigators evaluated the impact on the quality of life between patients who received nivolumab and those who received placebo and found no significant differences. Overall survival data is pending.

In view of the positive results from the CheckMate-274 trial, nivolumab has the potential to change the future of treatment for muscle-invasive urothelial carcinoma. These results support adjuvant nivolumab as a new standard of care for patients with high-risk muscle-invasive urothelial carcinoma after radical surgery regardless of PD-L1 status and previous neoadjuvant chemotherapy. Additional trials are yielding more data on the benefit of adjuvant immunotherapy in patients with high-risk muscle-invasive urothelial carcinoma.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


  1. Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021;384(22):2102–14. PMID: 34077643

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