The US Food and Drug Administration (FDA) today approved nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during a period of up to 1 year after first-line platinum-containing chemotherapy.
The accelerated approval makes nivolumab, which is a programmed cell death receptor–1 inhibitor, the second immunotherapy approved in this setting in the past year. The agency approved atezolizumab (Tecentriq, Genentech/Roche), which acts as a programmed cell death ligand–1 inhibitor, in May 2016.
Both nivolumab and atezolizumab received an accelerated approval on the basis of response rates; data on other outcomes, including survival, are awaited.
Urothelial carcinoma is the most common type of bladder cancer.
The drugs offer clinicians new options in metastatic bladder cancer after more than 30 years without a new drug therapy.
The new approval was based on a single-arm study in 270 patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression during or following platinum-containing chemotherapy, or whose disease progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Study patients received nivolumab, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity.
The objective response rate was 19.6% (53 of 270 patients; 95% confidence interval, 15.1 - 24.9). Seven patients had complete responses, and 46 had partial responses. The estimated median duration of response was 10.3 months. The FDA notes that some responses were ongoing at data cutoff.
Responses were confirmed by an independent radiographic review committee using Response Evaluation Criteria in Solid Tumors 1.1.
The most common adverse reactions (reported in 20% or fewer patients) were fatigue, musculoskeletal pain, nausea, and decreased appetite.
Fourteen patients died from causes other than disease progression. These patients included four who died from pneumonitis or cardiovascular failure attributed to nivolumab. Adverse reactions led to dose discontinuation in 17% of patients.
For this nivolumab application, the FDA granted a breakthrough therapy designation and priority review status. The application was approved about 1 month ahead of schedule.