What is the recommended use and dosage of Opdivo (nivolumab) in cancer treatment?

Recommended Use and Dosage of Opdivo (Nivolumab) in Cancer Treatment

Opdivo (nivolumab) is recommended as monotherapy at a dose of 240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously until disease progression or unacceptable toxicity for most cancer indications, with specific combination regimens and treatment durations varying by cancer type. 1

Approved Indications

Melanoma

• For unresectable or metastatic melanoma (both BRAF wild-type and BRAF-mutant):
  • Nivolumab monotherapy: 240 mg IV every 2 weeks or 480 mg IV every 4 weeks until disease progression or unacceptable toxicity 2
  • Nivolumab plus ipilimumab: Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg IV every 3 weeks for 4 doses, followed by nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks until disease progression or unacceptable toxicity 2
  • Nivolumab plus relatlimab: Relatlimab 160 mg and nivolumab 480 mg IV once every 4 weeks until progression 2

Adjuvant Treatment

• For adjuvant treatment of melanoma: Nivolumab 240 mg IV every 2 weeks or 480 mg IV every 4 weeks for 52 weeks 2
• For adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer: 240 mg IV every 2 weeks or 480 mg IV every 4 weeks until disease progression or unacceptable toxicity for a total treatment duration of 1 year 1

Other Solid Tumors

• For MSI-H/dMMR metastatic colorectal cancer: 240 mg IV every 2 weeks or 480 mg IV every 4 weeks until disease progression or unacceptable toxicity 1, 3
• For hepatocellular carcinoma (in combination with ipilimumab): Follow combination dosing regimen 1
• For esophageal cancer, gastric cancer, and gastroesophageal junction cancer: 240 mg IV every 2 weeks or 360 mg IV every 3 weeks in combination with chemotherapy 1

Dosage Evolution and Rationale

• Original clinical trials used weight-based dosing (3 mg/kg every 2 weeks), but FDA-approved dosing has evolved to fixed dosing (240 mg every 2 weeks or 480 mg every 4 weeks) based on pharmacokinetic modeling 2, 4
• The flat dose of 240 mg was selected based on equivalence to the 3 mg/kg dose at the median body weight of approximately 80 kg in the nivolumab clinical program 4
• Pharmacokinetic studies demonstrated that the benefit-risk profile of nivolumab 240 mg Q2W is comparable to 3 mg/kg Q2W across different body weights and tumor types 4

Treatment Duration Considerations

• FDA prescribing information recommends treatment until disease progression or unacceptable toxicity 1
• Clinical trials have shown that responses to nivolumab are often durable and may persist for years beyond treatment discontinuation 2
• Some responses to anti-PD-1 therapy may take time to develop, with some patients experiencing initial progression before responding 2
• For adjuvant therapy, treatment is typically administered for a fixed duration (e.g., 52 weeks for melanoma) 2

Dosage Modifications

• No dose reduction for nivolumab is recommended 1
• Withhold nivolumab for severe (Grade 3) immune-mediated adverse reactions 1
• Permanently discontinue for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe immune-mediated reactions, or inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks 1

Efficacy and Safety Considerations

• Nivolumab has demonstrated improved overall survival compared to chemotherapy in multiple cancer types 2, 5
• In melanoma, nivolumab showed objective response rates of 25-31.7% with durable responses 2, 6
• Safety analyses have not demonstrated a clinically meaningful relationship between body weight or nivolumab exposure and frequency or severity of adverse events 4
• Common immune-mediated adverse reactions include pneumonitis, colitis, hepatitis, nephritis, and endocrinopathies 1

Practical Considerations

• Flat dosing regimens simplify preparation time and improve ease of administration compared to weight-based dosing 4
• When nivolumab is administered in combination with ipilimumab, both drugs should be withheld or permanently discontinued for adverse reactions meeting dose modification guidelines 1
• Appropriate monitoring for disease progression is necessary regardless of dosing schedule 2