Adjuvant nivolumab approved in Europe for muscle-invasive urothelial carcinoma

The European Commission has approved nivolumab (Opdivo) for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection.1

The approval was based on results from the randomized, double-blind phase 3 CheckMate-274 trial (NCT02632409), which evaluated nivolumab (n =353) vs placebo (n = 356).2,3 Patients who received nivolumab had a median disease-free survival of 20.8 months (95% CI, 16.5 to 27.6) vs 10.8 months (95% CI, 8.3 to 13.9) in the placebo arm (HR, 0.70; 95% CI, 0.57-0.86; P =.0008).

Moreover, investigators reported that 74.5% of patients in the nivolumab arm who had a PD-L1 expression of 1% or higher were alive and disease-free at 6-months vs 55.7% of those in the placebo (HR, 0.55; P <.001). A subgroup analysis identified a higher probability of DFS following treatment with nivolumab vs placebo regardless of nodule or PD-L1 status or use or non-use of previous neoadjuvant chemotherapy. At the database lock, 83.6% of patients were still receiving nivolumab or the placebo.

“For years, patients with muscle-invasive urothelial carcinoma have lived with the unfortunate reality that, despite being diagnosed early enough to have their cancer removed, around half will face disease recurrence, with few safe and effective treatment options available to help prevent this cycle,” Fred Witjes, MD, professor of oncological urology, Radboud Institute for Molecular Life Sciences, stated in a news release.

“With the approval of nivolumab, clinicians will now have an immunotherapy treatment option to offer certain patients after surgery that, in the CheckMate -274 clinical trial, significantly reduced the risk of disease recurrence or death. This approval has the potential to transform the way we treat muscle-invasive urothelial carcinoma for appropriate patients in the European Union,” added Witjes.

Additional findings from CheckMate-274 showed a median survival free from recurrence outside of the urothelial tract of 22.9 months for the nivolumab ITT population and 13.7 months for the placebo ITT population. At the 6-month follow-up, 77.0% in the nivolumab group and 62.7% in the placebo group were alive and disease free (HR, 0.72. Among patients who had a PD-L1 expression of 1% or more, 75.3% in the nivolumab group and 56.7% in the placebo group were alive and free from recurrence outside the urothelial tract at 6 months (HR, 0.55).

Treatment with nivolumab also yielded a longer median distant metastasis-free survival (MFS) of 40.5 months, and 29.5 months for the placebo group. Investigators also reported a 6-month distant MFS of 82.5% and 69.8% in both the nivolumab and placebo cohort, respectively (HR, 0.75). Those who had a PD-L1 expression of 1% or more had a 6-month distant MFS of 78.7% and 65.7% in both groups, respectively (HR, 0.61).

Adverse effects (AEs) occurred in 98.9% of patients who were treated with adjuvant nivolumab and 95.4% of those who received the placebo. AEs that were grade 3 or higher occurred in 42.7% of patients in the nivolumab arm and 36.8% in the placebo arm.

The US FDA approved nivolumab for this indication in August 2021.


1. Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) as Adjuvant Treatment for Patients with Radically Resected, High-Risk Muscle-Invasive Urothelial Carcinoma with Tumor Cell PD-L1 Expression ≥1%. Published online April 5, 2022. Accessed April 5, 2022.

2. U.S. Food and Drug Administration approves Opdivo (nivolumab) for the adjuvant treatment of patients with high-risk urothelial carcinoma. News release. Bristol Myers Squibb. August 20, 2021. Accessed August 20, 2021.

3. Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384(22):2102-2114. doi:10.1056/NEJMoa2034442.