August 2021: Nivolumab (Opdivo, Bristol-Myers Squibb Co.) has been approved by the Food and Drug Administration for the adjuvant treatment of patients with urothelial carcinoma (UC) who are at high risk of recurrence following radical resection.
This is the first time the FDA has approved an adjuvant treatment for high-risk UC patients. The findings also backed up the decision to convert nivolumab’s accelerated authorisation for advanced/metastatic UC to a standard approval.
Nivolumab was studied in CHECKMATE-274 (NCT02632409), a randomised, double-blind, placebo-controlled trial in patients with UC of the bladder or upper urinary tract (renal pelvis or ureter) who were at high risk of recurrence within 120 days of radical resection. Patients were randomly assigned (1:1) to receive nivolumab 240 mg or placebo by intravenous infusion every two weeks until recurrence or intolerable toxicity, with a maximum treatment period of one year.
In the intent-to-treat (ITT) group and in patients with tumours expressing PD-L1 less than 1%, the primary effectiveness objective was investigator-assessed disease-free survival (DFS). Time to first recurrence (local urothelial tract, local non-urothelial tract, or distant metastatic) or death was used to determine DFS. For all primary objectives, a statistically significant improvement in DFS was reported in participants on the nivolumab arm vs. placebo at a prespecified interim analysis. In the ITT analysis, patients who got nivolumab had a median DFS of 20.8 months (95 percent CI: 16.5, 27.6) compared to 10.8 months (95 percent CI: 8.3, 13.9) in patients who received placebo (HR 0.70; 95 percent CI: 0.57, 0.86; p=0.0008). Patients who received nivolumab had a median DFS of not achieved (95 percent confidence interval: 21.2, not estimable) compared to 8.4 months (95 percent confidence interval: 5.6, 21.2) for those who got placebo (HR 0.55; 95 percent confidence interval: 0.39, 0.77; p=0.0005).
The unstratified DFS hazard ratio estimate was 0.83 in an exploratory examination of patients with PD-L1-negative tumours (58 percent) (95 percent CI: 0.64, 1.08). With 33 percent of deaths in the entire randomised population, OS data is still in its infancy. There were 37 deaths in the UTUC subpopulation (20 in the nivolumab arm, 17 in the placebo arm).
Rashes, weariness, diarrhoea, pruritus, musculoskeletal pain, and urinary tract infection were the most prevalent adverse effects observed in approximately 20% of participants who received nivolumab in CHECKMATE-274.
Nivolumab is prescribed at a dose of 240 mg every two weeks or 480 mg every four weeks for the adjuvant treatment of UC.
Verwysing: https://www.fda.gov/
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