On March 6, 2024, nivolumab (Opdivo) was approved for use in combination with cisplatin and gemcitabine for first-line treatment of patients with unresectable or metastatic urothelial carcinoma.¹

Supporting Efficacy Data

Approval was based on the open-label CheckMate 901 trial ­(ClinicalTrials.gov identifier NCT03036098), in which 608 patients were randomly assigned to receive nivolumab in combination with cisplatin plus gemcitabine for up to six cycles followed by nivolumab for up to 2 years (n = 304) or cisplatin plus gemcitabine for up to six cycles. In both groups, patients discontinuing cisplatin alone were permitted to receive ­carboplatin. Randomization was stratified by tumor PD-L1 expression and presence of liver metastasis.

Median overall survival was 21.7 months (95% confidence interval [CI] = 18.6–26.4 months) in the nivolumab-plus-chemotherapy group vs 18.9 months (95% CI = 14.7–22.4 months) in the chemotherapy-alone group (hazard ratio [HR] = 0.78, 95% CI = 0.63–0.96, P = .0171). Median progression-free survival on blinded independent central review was 7.9 months (95% CI = 7.6–9.5 months) in the nivolumab group vs 7.6 months (95% CI = 6.0–7.8 months) in the chemotherapy-alone group (HR = 0.72, 95% CI = 0.59–0.88, P = .0012).

How It Is Used

The recommended nivolumab dose for this indication follows:

• 360 mg every 3 weeks in combination with cisplatin and gemcitabine every 3 weeks for up to six 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 of 2 years from the first dose.

Safety Profile

In CheckMate 901, the most common adverse events of any grade in the nivolumab-plus-chemotherapy group were nausea (52% vs 53% in the control group), fatigue (48% vs 43%), musculoskeletal pain (33% vs 21%), constipation (30% vs 28%), decreased appetite (30% vs 19%), rash (25% vs 7%), vomiting (23% vs 19%), and peripheral neuropathy (20% vs 14%). The most common grade 3 or 4 adverse events in the nivolumab group included urinary tract infection (8% vs 8%), renal dysfunction (6% vs 2%), and fatigue (4% vs 4%).

Serious adverse events occurred in 48% of patients in the nivolumab-plus-chemotherapy group, most commonly urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decrease (2.3%). Adverse events led to discontinuation of nivolumab or chemotherapy in 30% of patients. Fatal adverse reactions occurred in 3.6% of patients in the nivolumab-plus-chemotherapy group, including sepsis in 1%.

Nivolumab has warnings/precautions for immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, and nephritis and renal dysfunction; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving nivolumab. 

REFERENCE

1. Opdivo (nivolumab) injection, for intravenous use, prescribing information, Bristol-Myers Squibb Company, March 2024. Available at https://www.opdivohcp.com. Accessed March 21, 2024.