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

Full prescribing information for nivolumab can be viewed here.

Efficacy was evaluated in CHECKMATE-901 (NCT03036098), a randomised, open-label trial enrolling 608 patients with previously untreated unresectable or metastatic UC. Patients were randomised (1:1) to receive either nivolumab in combination with cisplatin and gemcitabine (up to 6 cycles) followed by nivolumab alone for up to two years or cisplatin and gemcitabine (up to 6 cycles). On both arms, patients discontinuing cisplatin were permitted to receive carboplatin. Randomisation was stratified by tumour 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 who received nivolumab in combination with cisplatin and gemcitabine and 18.9 months (95% CI: 14.7, 22.4) for those who received cisplatin and gemcitabine alone, (hazard ratio [HR] 0.78 [95% CI: 0.63, 0.96]; two-sided p-value 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-value 0.0012).

The most common adverse reactions (≥15%) in patients receiving nivolumab with platinum-doublet chemotherapy were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhoea, oedema, hypothyroidism, and pruritis.

The recommended nivolumab dose for this indication is:

360 mg every 3 weeks in combination with cisplatin and gemcitabine every 3 weeks for up to 6 cycles followed by

240 mg every 2 weeks or 480 mg every 4 weeks as a single agent until disease progression, unacceptable toxicity, or a maximum treatment of 2 years from first dose.

Source: FDA