FDA approves Opdivo as adjuvant treatment of high-risk urothelial carcinoma
The FDA approved nivolumab for adjuvant treatment of patients with surgically resected, high-risk urothelial carcinoma, according to the agent’s manufacturer.
The approval of nivolumab (Opdivo, Bristol Myers Squibb), a PD-1 immune checkpoint inhibitor, applies to patients regardless of previous chemotherapy, nodal involvement or PD-L1 status.
“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 [cancer] returning,” Matthew D. Galsky, MD, professor of medicine, director of genitourinary medical oncology, co-director of the Center of Excellence for Bladder Cancer, and associate director for translational research at The Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, said in a Bristol Myers Squibb-issued press release. “Nivolumab provides a new FDA-approved treatment shown to reduce the risk [for] 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.”
The randomized phase 3 CheckMate-274 trial included 709 patients with muscle-invasive urothelial cancer at high risk for recurrence after radical surgery. Galsky and colleagues randomly assigned patients 1:1 to 240 mg nivolumab (n = 353) or placebo (n = 356) every 2 weeks for up to 1 year, or until disease recurrence or unacceptable toxicity.
Investigator-assessed DFS among all patients, as well as in the subgroup with tumor PD-L1 expression of 1% or greater, served as major efficacy outcome measures. Researchers also assessed OS.
As Healio previously reported, results showed nivolumab nearly doubled DFS compared with placebo (median, 20.8 months vs. 10.8 months), reducing risk for disease recurrence or death by 30% (HR = 0.7; 95% CI, 0.57-0.86). Median DFS among patients with PD-L1 expression of at least 1% was not reached with nivolumab vs. 8.4 months with placebo, for a reduction in risk for recurrence or death of 45% (HR = 0.55; 95% CI, 0.39-0.77).
The most common adverse events among patients who received nivolumab included rash (36%), fatigue (36%), diarrhea (30%), pruritus (30%), musculoskeletal pain (28%) and urinary tract infection (22%). Thirty percent of patients in the nivolumab group experienced serious adverse reactions, the most frequent of which was urinary tract infection. Fatal adverse events, including pneumonitis, occurred among 1% of patients.
The FDA previously approved nivolumab for several cancer-related indications, including as adjuvant treatment of certain patients with melanoma and esophageal or gastroesophageal junction cancer.
“[Urothelial carcinoma] is the third type of cancer where Opdivo has been the first approved PD-1 inhibitor in the adjuvant setting,” Adam Lenkowsky, senior vice president and general manager of U.S. cardiovascular, immunology and oncology at Bristol Myers Squibb, said in the press release. “Now with this advancement, we can offer new hope to the conversations between health care providers and their [patients with urothelial carcinoma] where historically no approved treatment options have existed to help prevent disease recurrence post-surgery.”