What is the recommended dose of Nivolumab (Opdivo) for cancer treatment?

Recommended Dosing of Nivolumab (Opdivo) for Cancer Treatment

The recommended dosage of nivolumab (Opdivo) for cancer treatment is 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks, with specific regimens varying by cancer type and whether used as monotherapy or in combination therapy. 1, 2

Standard Dosing Regimens

Monotherapy Options:

• 240 mg IV every 2 weeks 1, 3, 2
• 480 mg IV every 4 weeks 1, 3, 2
• 3 mg/kg IV every 2 weeks (weight-based dosing) 1

Combination Therapy with Ipilimumab:

• Induction phase: Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for 4 doses
• Maintenance phase: Nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks 1, 3

Cancer-Specific Dosing

Melanoma

• Monotherapy: 240 mg every 2 weeks, 480 mg every 4 weeks, or 3 mg/kg every 2 weeks 1
• With ipilimumab: Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for 4 doses, followed by nivolumab monotherapy 1

Colorectal Cancer (dMMR/MSI-H only)

• 240 mg every 2 weeks or 480 mg every 4 weeks
• For pediatric patients ≥12 years and ≥40 kg: 240 mg every 2 weeks or 480 mg every 4 weeks
• For pediatric patients ≥12 years and <40 kg: 3 mg/kg every 2 weeks 1, 2

Administration Guidelines

• Administer as an intravenous infusion over 30 minutes 3
• Dilute with either 0.9% Sodium Chloride or 5% Dextrose to a final concentration between 1-10 mg/mL 3
• When administering in combination with other therapies, nivolumab should be administered first 3

Duration of Treatment

Treatment duration varies by indication:

• Until disease progression or unacceptable toxicity (most indications) 2
• For adjuvant treatment: Up to 1 year or 2 years depending on the cancer type 2

Dosage Modifications

• No dose reduction is recommended for nivolumab 2
• Consider withholding for severe (Grade 3) immune-mediated adverse reactions
• Permanently discontinue for life-threatening (Grade 4) immune-mediated adverse reactions 2

Evidence Supporting Fixed Dosing

The transition from weight-based dosing (3 mg/kg) to fixed dosing (240 mg Q2W or 480 mg Q4W) is supported by pharmacokinetic modeling and exposure-response analyses 4. The 480 mg Q4W dosing provides similar efficacy to 3 mg/kg Q2W with:

• Similar time-averaged steady-state concentrations (only 5.2% higher) 4
• Higher maximum concentration (Cmax) after first dose (110.4% higher), but still below the established safe dose of 10 mg/kg Q2W 4
• Lower trough concentration at day 28 (22.1% lower) 4

Clinical Considerations

• The 480 mg Q4W regimen offers greater convenience with fewer clinic visits while maintaining similar efficacy and safety profiles 4, 5
• Real-world data show similar safety profiles between 240 mg Q2W and 480 mg Q4W dosing regimens 5
• Receptor occupancy is saturated at doses ≥0.3 mg/kg, supporting the efficacy of fixed dosing regimens 6

Potential Pitfalls

• Immune-related adverse events can occur at any dose, requiring vigilant monitoring regardless of dosing regimen 7
• Rare cases of severe immune-related adverse events have been reported with the 480 mg dose after previous tolerance to lower doses 7
• Dose-response relationships may vary slightly by tumor type, with NSCLC potentially benefiting from doses ≥3 mg/kg compared to lower doses 6

The selection of the appropriate nivolumab dosing regimen should consider the specific cancer type, combination therapy requirements, and patient convenience factors, with the fixed dosing regimens (240 mg Q2W or 480 mg Q4W) now established as standard approaches across multiple cancer types.