Drug Detail:Nivolumab (Nivolumab [ nye-vol-ue-mab ])
Drug Class: Anti-PD-1 and PD-L1 monoclonal antibodies (immune checkpoint inhibitors)
Usual Adult Dose for Melanoma - Metastatic
MONOTHERAPY:
UNRESECTABLE OR METASTATIC MELANOMA:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
ADJUVANT TREATMENT OF MELANOMA:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity for up to one year
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity for up to one year
IN COMBINATION WITH IPILIMUMAB:
UNRESECTABLE OR METASTATIC MELANOMA:
1 mg/kg IV over 30 minutes every 3 weeks with ipilimumab 3 mg/kg IV over 90 minutes on the same day for a maximum of 4 doses or until unacceptable toxicity, whichever occurs earlier
THEN:
240 mg IV over 30 minutes every 2 weeks; after completing 4 doses of combination therapy, administer as single agent until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks; after completing 4 doses of combination therapy, administer as single agent until disease progression or unacceptable toxicity
Uses:
- This drug, as a single agent or in combination with ipilimumab, is indicated for the treatment of patients with unresectable or metastatic melanoma
- For the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection
Usual Adult Dose for Non-Small Cell Lung Cancer
MONOTHERAPY:
METASTATIC NON-SMALL CELL LUNG CANCER:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
IN COMBINATION WITH IPILIMUMAB:
METASTATIC OR RECURRENT NON-SMALL CELL LUNG CANCER EXPRESSING PD-L1:
3 mg/kg IV over 30 minutes every 2 weeks with ipilimumab 1 mg/kg IV over 30 minutes every 6 weeks until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression
METASTATIC OR RECURRENT NON-SMALL CELL LUNG CANCER:
360 mg IV over 30 minutes every 3 weeks with ipilimumab 1 mg/kg IV over 30 minutes every 6 weeks and histology-based platinum doublet chemotherapy every 3 weeks for the first 2 cycles, then 360 mg IV over 30 minutes every 3 weeks with ipilimumab 1 mg/kg IV over 30 minutes every 6 weeks until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression
Comments:
- Select patients with metastatic NSCLC for treatment with this drug in combination with ipilimumab based on PD-L1 expression.
Uses:
- This drug, in combination with ipilimumab, is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (1% or greater) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations
- This drug, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations
- For the treatment of patients with metastatic NSCLC with progression on or after platinum-based chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving this drug
Usual Adult Dose for Malignant Pleural Mesothelioma
IN COMBINATION WITH IPILIMUMAB:
360 mg IV over 30 minutes every 3 weeks with ipilimumab 1 mg/kg IV over 30 minutes every 6 weeks until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression
Use: This drug, in combination with ipilimumab, is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma
Usual Adult Dose for Renal Cell Carcinoma
MONOTHERAPY:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
IN COMBINATION WITH IPILIMUMAB:
3 mg/kg IV over 30 minutes every 3 weeks with ipilimumab 1 mg/kg IV over 30 minutes on the same day for 4 doses
THEN AFTER COMPLETING 4 DOSES OF COMBINATION THERAPY, ADMINISTER AS SINGLE AGENT:
240 mg IV over 30 minutes every 2 weeks until disease progression, unacceptable toxicity, or up to 2 years
OR
480 mg IV over 30 minutes every 4 weeks until disease progression, unacceptable toxicity, or up to 2 years
IN COMBINATION WITH CABOZANTINIB:
240 mg IV over 30 minutes every 2 weeks in combination with cabozantinib 40 mg orally once daily (without food) until disease progression or unacceptable toxicity
OR
240 mg IV over 30 minutes every 2 weeks in combination with cabozantinib 40 mg orally once daily (without food) until disease progression or unacceptable toxicity
NOTE: After completing 4 doses of combination therapy with ipilimumab, administer nivolumab as single agent until disease progression or unacceptable toxicity.
Uses:
- As a single agent for treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy
- In combination with ipilimumab for first-line treatment of intermediate or poor risk advanced RCC
- In combination with cabozantinib the first-line treatment of patients with advanced RCC
Usual Adult Dose for Hodgkin's Disease
MONOTHERAPY:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
Use: For classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin OR 3 or more lines of systemic therapy that includes autologous HSCT
Usual Adult Dose for Head and Neck Cancer
MONOTHERAPY:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
Use: For recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy
Usual Adult Dose for Urothelial Carcinoma
MONOTHERAPY:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
Use: For locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
Usual Adult Dose for Colorectal Cancer
MONOTHERAPY:
40 KG OR GREATER:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
IN COMBINATION WITH IPILIMUMAB:
40 KG OR GREATER:
3 mg/kg IV over 30 minutes every 3 weeks with ipilimumab 1 mg/kg IV over 30 minutes on the same day for a total of 4 doses
AFTER COMPLETING 4 DOSES OF COMBINATION THERAPY, ADMINISTER AS SINGLE AGENT:
40 KG OR GREATER:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
Use: As a single agent or in combination with ipilimumab for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
Usual Adult Dose for Hepatocellular Carcinoma
MONOTHERAPY:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
IN COMBINATION WITH IPILIMUMAB:
1 mg/kg IV over 30 minutes every 3 weeks with ipilimumab 3 mg/kg IV over 30 minutes on the same day for 4 doses
THEN AFTER COMPLETING 4 DOSES OF COMBINATION THERAPY, ADMINISTER AS SINGLE AGENT:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
Use: As a single agent or in combination with ipilimumab for hepatocellular carcinoma (HCC) who have been previously treated with sorafenib
Usual Adult Dose for Esophageal Carcinoma
MONOTHERAPY:
240 mg IV over 30 minutes every 2 weeks until disease progression, unacceptable toxicity, or for a total treatment duration of 1 year
OR
480 mg IV over 30 minutes every 4 weeks until disease progression, unacceptable toxicity, or for a total treatment duration of 1 year
IN COMBINATION:
240 mg IV over 30 minutes every 2 weeks with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks until disease progression, unacceptable toxicity, or up to 2 years
OR
360 mg IV over 30 minutes every 3 weeks with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks until disease progression, unacceptable toxicity, or up to 2 years
Uses:
- For the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT)
- For the treatment of patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy
- In combination with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma
Usual Adult Dose for Gastric Cancer
MONOTHERAPY:
240 mg IV over 30 minutes every 2 weeks until disease progression, unacceptable toxicity, or for a total treatment duration of 1 year
OR
480 mg IV over 30 minutes every 4 weeks until disease progression, unacceptable toxicity, or for a total treatment duration of 1 year
IN COMBINATION:
240 mg IV over 30 minutes every 2 weeks with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks until disease progression, unacceptable toxicity, or up to 2 years
OR
360 mg IV over 30 minutes every 3 weeks with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks until disease progression, unacceptable toxicity, or up to 2 years
Uses:
- For the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT)
- For the treatment of patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy
- In combination with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma
Usual Pediatric Dose for Colorectal Cancer
MONOTHERAPY:
12 years and older:
LESS THAN 40 KG:
3 mg/kg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
12 years and older:
40 KG OR GREATER:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
IN COMBINATION WITH IPILIMUMAB:
12 years and older:
3 mg/kg IV over 30 minutes every 2 weeks with ipilimumab 1 mg/kg IV over 30 minutes on the same day for a total of 4 doses
AFTER COMPLETING 4 DOSES OF COMBINATION THERAPY, ADMINISTER AS SINGLE AGENT:
LESS THAN 40 KG:
3 mg/kg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
40 KG OR GREATER:
240 mg IV over 30 minutes every 2 weeks until disease progression or unacceptable toxicity
OR
480 mg IV over 30 minutes every 4 weeks until disease progression or unacceptable toxicity
Use: As a single agent or in combination with ipilimumab for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan in pediatric patients 12 years and older
Renal Dose Adjustments
No adjustment recommended.
Liver Dose Adjustments
Mild hepatic impairment: No adjustment recommended.
Moderate to severe hepatic impairment: Data not available
Dose Adjustments
NOTE:
- No dose reduction for nivolumab is recommended. In general, withhold therapy for severe (Grade 3) immune-mediated adverse reactions.
- Permanently discontinue therapy for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids.
- When nivolumab is administered in combination with ipilimumab, if nivolumab is withheld, ipilimumab should also be withheld.
- There are no recommended dose modifications for hypothyroidism or hyperthyroidism.
- Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions.
- Discontinue therapy in patients with severe or life-threatening infusion reactions.
RECOMMENDED DOSE MODIFICATIONS FOR NIVOLUMAB AS A SINGLE AGENT:
PNEUMONITIS:
- Grade 2: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
- Grade 3 or 4 pneumonitis: Permanently discontinue therapy; administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents, followed by a corticosteroid taper
- Grade 2 or 3: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
- Grade 4: Permanently discontinue therapy.
- If aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is more than 3 and up to 8 times upper limit of normal (ULN) OR total bilirubin is more than 1.5 and up to 3 x ULN: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
- If AST or ALT is more than 8 x ULN OR total bilirubin is more than 3 x ULN: Permanently discontinue therapy.
- Baseline AST/ALT is more than 1 and up to 3 x ULN and increases to more than 5 and up to 10 x ULN OR baseline AST/ALT is more than 3 and up to 5 x ULN and increases to more than 8 and up to 10 x ULN: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
- AST/ALT increases to more than 10 x ULN OR total bilirubin increases to more than 3 x ULN: Permanently discontinue therapy.
- Grade 3 or 4: Withhold therapy until stable or permanently discontinue depending on severity.
- Grade 2 or 3 increased blood creatinine: : Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
- Grade 4 increased blood creatinine: Permanently discontinue therapy.
- Suspected Stevens Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS): Withhold therapy.
MYOCARDITIS:
- Grade 2, 3, or 4: Permanently discontinue therapy.
- Grade 2: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
- Grade 3 or 4: Permanently discontinue therapy.
- Grade 1 or 2: Interrupt or slow the rate of infusion.
- Grade 3 or 4: Permanently discontinue therapy.
RECOMMENDED DOSE MODIFICATIONS FOR COMBINATION THERAPY:
COLITIS:
- Grade 2: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
- Grade 3 or 4: Permanently discontinue therapy.
- AST/ALT increases to more than 3 and up to 5 x ULN OR total bilirubin increases to more than 1.5 and up to 3 x ULN: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
- AST or ALT more than 5 x ULN OR total bilirubin more than 3 times ULN: Permanently discontinue therapy.
- Baseline AST/ALT is more than 1 and up to 3 x ULN and increases to more than 5 and up to 10 x ULN OR baseline AST/ALT is more than 3 and up to 5 x ULN and increases to more than 8 and up to 10 x ULN: Withhold therapy; resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper; permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.
- AST/ALT increases to more than 10 x ULN OR total bilirubin increases to more than 3 x ULN: Permanently discontinue therapy.
Precautions
CONTRAINDICATIONS:
- None
Safety and efficacy have not been established in patients younger than 12 years for colorectal cancer.
Safety and efficacy have not been established in patients younger than 18 years for all indications except colorectal cancer.
Consult WARNINGS section for additional precautions.
Dialysis
Data not available
Other Comments
Administration Advice:
- Use sterile, non-pyrogenic, low protein binding in-line filter with a 0.2 to 1.2 micrometer pore.
- Flush IV line after infusion.
- When this drug is administered in combination with ipilimumab, infuse this drug first followed by ipilimumab on the same day. Use separate infusion bags and filters for each infusion.
- When this drug is administered in combination with ipilimumab, if this drug is withheld, ipilimumab should also be withheld.
- Manufacturer prescribing information should be consulted for more information on ipilimumab dosing.
Reconstitution/preparation techniques:
- Dilute the drug with either normal saline or 5% dextrose to a concentration of 1 to 10 mg/mL.
- Invert to mix; do not shake.
Storage requirements:
- Refrigerate; protect from light; store in original package until use.
- After preparation, keep at room temperature for no more than 4 hours or in the refrigerator for no more than 24 hours, include infusion time.
- Do not freeze.
IV compatibility:
- Do not coadminister other drugs through the same line.
Monitoring:
- Hepatic: Liver function tests prior to initiating therapy and periodically thereafter
- Renal: Serum creatinine prior to initiating therapy and periodically thereafter
- Endocrine: Thyroid function prior to initiating therapy and periodically thereafter
Patient Education:
- Inform patients about the risk of immune-mediated reactions that may occur and lead to disruption or discontinuation of therapy and corticosteroid treatment.
- Advise females of reproductive age to use effective contraception during treatment and for at least 5 months after the last dose.
- Advise women against breastfeeding while taking this drug.
- Inform patients about the importance of having regular blood work and lab tests done while taking this drug.
Frequently asked questions
- Pembrolizumab vs. nivolumab: how do they compare?
