FDA approves nivolumab in combination with cisplatin and gemcitabine for unresectable or metastatic urothelial carcinoma

Regulatory approval: On March 7, 2024, the FDA approved nivolumab plus cisplatin and gemcitabine for first-line treatment of adults with unresectable or metastatic urothelial carcinoma. The decision was based on CHECKMATE-901 (NCT03036098; n=608), which showed statistically significant improvements in overall survival and progression-free survival versus cisplatin/gemcitabine alone. Median OS was 21.7 vs 18.9 months (HR 0.78), and median PFS was 7.9 vs 7.6 months (HR 0.72).

FDA approval (March 7, 2024)

The FDA approved nivolumab (Opdivo) in combination with cisplatin and gemcitabine for first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma.

Supporting evidence: CHECKMATE-901

Efficacy was evaluated in CHECKMATE-901 (NCT03036098), a randomized, open-label trial enrolling 608 patients with previously untreated unresectable or metastatic urothelial carcinoma. Patients were randomized 1:1 to:

  • Nivolumab + cisplatin/gemcitabine (up to 6 cycles) followed by nivolumab alone for up to 2 years, or
  • Cisplatin/gemcitabine (up to 6 cycles).

On both arms, patients discontinuing cisplatin could receive carboplatin. Randomization was stratified by tumor PD-L1 expression and presence of liver metastasis.

Major endpoints were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (RECIST v1.1). Statistically significant benefits were reported:

  • OS: 21.7 vs 18.9 months (HR 0.78; 95% CI 0.63–0.96; p=0.0171)
  • PFS: 7.9 vs 7.6 months (HR 0.72; 95% CI 0.59–0.88; p=0.0012)

Safety and dosing (label information)

Common adverse reactions (≥15%) with nivolumab + platinum-doublet chemotherapy included nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, UTI, diarrhea, edema, hypothyroidism, and pruritis.

Recommended dosing: nivolumab 360 mg q3w with cisplatin/gemcitabine (q3w) for up to 6 cycles, then nivolumab 240 mg q2w or 480 mg q4w until progression, unacceptable toxicity, or a maximum of 2 years from first dose.

The review used Project Orbis and the FDA RTOR pilot; reviews at other participating agencies were noted as ongoing.

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