The Food and Drug Administration (FDA) has approved Opdivo® (nivolumab) for the adjuvant treatment of patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection, regardless of prior neoadjuvant chemotherapy, nodal involvement or PD-L1 status.
The approval was based on data from the multicenter, randomized, double-blind, placebo-controlled phase 3 CheckMate-274 trial (ClinicalTrials.gov Identifier: NCT02632409) which evaluated the efficacy and safety of nivolumab as an adjuvant treatment in 699 adults who had undergone radical surgery for invasive urothelial carcinoma at high risk of recurrence. Patients were randomly assigned 1:1 to receive either nivolumab 240mg via intravenous infusion over 30 minutes every 2 weeks or placebo until recurrence or unacceptable toxicity for a maximum duration of 1 year.
The primary endpoint was disease-free survival (DFS), defined as the time between the date of randomization and the date of first recurrence (local urothelial tract, local non-urothelial tract, or distant metastasis) or death, from any cause. Key secondary endpoint included overall survival (OS).
Results showed that patients treated with nivolumab achieved a statistically significant improvement in median DFS of 20.8 months (95% CI, 16.5-27.6) vs 10.8 months for placebo. Nivolumab reduced the risk of disease recurrence or death by 30% vs placebo (hazard ratio [HR] 0.70; 95% CI, 0.57-0.86; P =.0008).
Among patients whose tumors expressed programmed death-ligand 1 (PD-L1) of at least 1%, the median DFS was not reached (95% CI, 21.2-not evaluable; n=140) in the nivolumab arm vs 8.4 months (95% CI, 5.6-21.2; n=142) in the placebo arm. Nivolumab reduced the risk of disease recurrence or death by 45% vs placebo (HR 0.55; 95% CI, 0.39-0.77; P =.0005).
“UC is the third type of cancer where Opdivo has been the first approved PD-1 inhibitor in the adjuvant setting. Now with this advancement, we can offer new hope to the conversations between healthcare providers and their UC patients where historically no approved treatment options have existed to help prevent disease recurrence post-surgery,” said Adam Lenkowsky, senior vice president and general manager, US Cardiovascular, Immunology and Oncology, Bristol Myers Squibb.
Additionally, in February 2017, the FDA granted accelerated approval to Opdivo for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or after platinum-based chemotherapy, or for those who have disease progression within 12 months of neoadjuvant or adjuvant platinum-based chemotherapy. The findings from the CheckMate-274 trial support the regular approval of Opdivo for this indication.
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. Accessed August 20, 2021. https://www.businesswire.com/news/home/20210820005285/en/U.S.-Food-and-Drug-Administration-Approves-Opdivo%C2%AE-nivolumab-for-the-Adjuvant-Treatment-of-Patients-with-High-Risk-Urothelial-Carcinoma.