PD-1 Inhibitor OK’d as Adjuvant Therapy for Bladder Cancer

The FDA has approved nivolumab (Opdivo) as an adjuvant therapy for patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection, regardless of prior neoadjuvant chemotherapy, nodal involvement, or PD-L1 status, Bristol Myers Squibb announced.

Nivolumab becomes the first PD-1 inhibitor in UC with an indication in the adjuvant setting. Approval was based on results from the phase III CheckMate-274 trial.

“This approval is a major milestone for patients who have undergone major surgery to remove the bladder or parts of the urinary tract and are in need of additional treatment approaches that can help reduce the risk of their UC returning,” said primary investigator Matthew Galsky, MD, of the Icahn School of Medicine at Mount Sinai in New York City, in a press release.

“Nivolumab provides a new FDA-approved treatment shown to reduce the risk of disease recurrence or death based on the safety and efficacy findings from CheckMate-274, and has the potential to become a new standard of care option in this setting,” he added.

The trial compared a 240-mg dose of nivolumab in 353 patients or placebo in 356 patients. Patients treated with nivolumab achieved a median disease-free survival (DFS) of 20.8 months versus 10.8 months with placebo, representing a 30% reduction in the risk for disease recurrence or death (HR 0.70, 95% CI 0.57-0.86).

Among patients whose tumors expressed PD-L1 ≥1%, the median DFS was not reached with nivolumab, compared with 8.4 months for placebo (HR 0.55, 95% CI 0.39-0.77).

The prescribing information for nivolumab notes that it may cause severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, and other immune-mediated adverse reactions.

Labeling also notes the risk of infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, embryo-fetal toxicity, and increased mortality in myeloma patients when added to a thalidomide analogue and dexamethasone.