On February 2, 2017, the U.S. Food and Drug Administration granted accelerated approval to nivolumab (OPDIVO, Bristol-Myers Squibb Company) for treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with a platinum-containing chemotherapy.
Approval was based on a single-arm study treating 270 patients with locally advanced or metastatic urothelial carcinoma who progressed during or following platinum-containing chemotherapy, or progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Patients received nivolumab, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. Objective response rate, confirmed by an independent radiographic review committee using Response Evaluation Criteria in Solid Tumors 1.1, was 19.6% (53/270; 95% CI: 15.1, 24.9). Seven patients had complete responses and 46 had partial responses. Estimated median response duration was 10.3 months with responses ongoing at data cutoff.
The most common adverse reactions (reported in at least 20% of patients) were fatigue, musculoskeletal pain, nausea, and decreased appetite. Fourteen patients died from causes other than disease progression, including four patients who died from pneumonitis or cardiovascular failure attributed to nivolumab. Adverse reactions led to dose discontinuation in 17% of patients.
The recommended dose and schedule for nivolumab for the above indication is 240 mg intravenously every 2 weeks.
FDA granted this nivolumab application breakthrough therapy designation and priority review status. This application was approved approximately one month before the goal date. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).