On March 6, 2024, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo®) in combination with cisplatin and gemcitabine for first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC).

FDA update

Efficacy was evaluated in CHECKMATE-901 (NCT03036098), a randomized, open-label trial enrolling 608 patients with previously untreated unresectable or metastatic UC. Patients were randomized 1:1 to receive up to six cycles of either nivolumab in combination with cisplatin and gemcitabine followed by nivolumab alone for up to two years or cisplatin and gemcitabine. On both arms, patients discontinuing cisplatin were permitted to receive carboplatin. Randomization was stratified by tumor PD-L1 expression and presence of liver metastasis.

The major efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), assessed by blinded independent central review using RECIST v1.1.

Statistically significant benefits in both OS and PFS were demonstrated for nivolumab in combination with cisplatin and gemcitabine followed by nivolumab compared to cisplatin and gemcitabine alone. Median OS was 21.7 months (95% CI = 18.6, 26.4) for patients in the nivolumab arm and 18.9 months (95% CI = 14.7, 22.4) for those who received cisplatin and gemcitabine alone (HR = 0.78; 95% CI = 0.63, 0.96; two-sided p = 0.0171). Median PFS was 7.9 months (95% CI = 7.6, 9.5) and 7.6 months (95% CI = 6.0, 7.8), respectively (HR = 0.72; 95% CI = 0.59, 0.88; two-sided p = 0.0012).

The most common adverse reactions reported in at least 15% of patients receiving nivolumab with platinum-doublet chemotherapy are nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritis.

The recommended nivolumab dose for first-line treatment of adult patients with unresectable or metastatic UC is:

  • 360 mg every three weeks in combination with cisplatin and gemcitabine every three weeks for up to six cycles
  • Then, 240 mg every two weeks or 480 mg every four weeks as a single agent for up to two years from the first dose or until patients experience disease progression or unacceptable toxicity


View the full prescribing information for nivolumab.

Nivolumab’s review for this indication was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration, Brazilian Health Regulatory Agency, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

The review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

FDA granted the application priority review. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.