Nivolumab

Nivolumab is a prescription drug indicated for the treatment of patients with metastatic non-small cell lung cancer (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 nivolumab.

• Nivolumab is also indicated for the treatment of patients with advanced renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck and urothelial carcinoma.
• Nivolumab is available under the following different brand names: Opdivo.

Dosage of Nivolumab:

Intravenous solution

• 40 mg/4 ml (10 mg/ml)
• 100 mg/10 ml (10 mg/ml)
• Further dilution required before administration

Dosing Considerations – Should be Given as Follows:

Safety and efficacy have not been established for pediatric use. Adult dosages only:

Melanoma

• Single-agent
• Indicated as a single agent for BRAF V600 wild-type or BRAF V600 mutation-positive unresectable or metastatic melanoma
• 240 mg intravenous every 2 weeks infused over 1 hour
• Continue until disease progression or unacceptable toxicity
• Combination with ipilimumab
• Indicated in combination with ipilimumab for the treatment of patients with BRAF unresectable or metastatic melanoma
• 1 mg/kg intravenous infused over 1 hour, followed by ipilimumab (3 mg/kg intravenous infused over 90 min) administer on the same day every 3 weeks for 4 doses
• Subsequent doses of nivolumab as a single agent are 240 mg intravenous every 2 weeks infused over 1 hour until disease progression or unacceptable toxicity

Non-Small Cell Lung Cancer

• Indicated for metastatic non-small cell lung cancer (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 nivolumab
• 240 mg intravenous every 2 weeks infused over 1 hour
• Continue until disease progression or unacceptable toxicity

Renal Cell Carcinoma

• Indicated for patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy
• 240 mg intravenous every 2 weeks infused over 1 hour
• Continue until disease progression or unacceptable toxicity

Hodgkin Lymphoma

• Indicated for classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin
• 3 mg/kg intravenous infused over 1 hour every 2 weeks until disease progression or unacceptable toxicity

Head and Neck Cancer

• Indicated for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after a platinum-based therapy
• 3 mg/kg intravenously every 2 weeks infused over 1 hour
• Continue until disease progression or unacceptable toxicity

Urothelial Carcinoma

• Indicated for locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
• 240 mg intravenously every 2 weeks infused over 1 hour
• Continue until disease progression or unacceptable toxicity

Dosage Modifications

• Infusion reactions: interrupt or slow infusion rate with mild or moderate reactions; discontinue if severe or life-threatening infusion reactions occur
• Hypothyroidism or hyperthyroidism: no recommended dose modifications
• Renal impairment: no dosage modifications are required
• Mild hepatic impairment: no dosage modifications required
• Moderate or severe hepatic impairment: not studied
• Note: When administered in combination with ipilimumab, if nivolumab is withheld, ipilimumab should also be withheld

Withhold for any of the following

• Grade 2 pneumonitis
• Grade 2 diarrhea or colitis
• Grade 3 diarrhea or colitis (single-agent nivolumab)
• Grade 2 or 3 hypophysitis
• Grade 2 adrenal insufficiency
• Grade 3 hyperglycemia
• Encephalitis, new-onset moderate or severe neurologic signs or symptoms
• Grade 3 rash or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
• AST or ALT over 3-5 times the upper limit of normal (ULN) or total bilirubin over 1.5-3 times ULN
• Serum creatinine over 1.5-6 times ULN or over 1.5 times baseline
• Any other severe or grade 3 treatment-related adverse reaction
• May resume treatment for patients whose adverse reactions recover to grade 0-1

Permanently discontinue for any of the following:

• Any life-threatening or grade 4 adverse reactions
• Grade 3 or 4 pneumonitis
• Grade 3 diarrhea or colitis (nivolumab in combination with ipilimumab)
• Grade 4 diarrhea or colitis
• Grade 4 hypophysitis
• Grade 3 or 4 adrenal insufficiency
• Grade 4 hyperglycemia
• Immune-mediated encephalitis
• Grade 4 rash or confirmed SJS or TEN
• AST or ALT over 5 times upper limit of normal (ULN) or total bilirubin over 3 times ULN
• Serum creatinine over 6 times ULN
• Any severe or grade 3 treatment-related adverse reaction that recurs
• Inability to reduce corticosteroid dose to up to 10 mg/day of prednisone or equivalent within 12 weeks
• Persistent grade 2 or 3 treatment-related adverse reactions that do not recover to grade 0-1 within 12 weeks after the last dose

Dosing Considerations

Melanoma

• Indications for melanoma (as a single agent for BRAF V600 mutation-positive or in combination with ipilimumab) were approved under accelerated approval based on tumor response rate and durability of response; continued approval may be contingent upon verification and description of clinical benefit in the confirmatory trials
• Information on FDA-approved tests for detection of PD-L1 expression in non-small-cell lung cancer (NSCLC) is available at: http://www.fda.gov/CompanionDiagnostics
• Classical Hodgkin lymphoma (cHL)
• Indication for cHL approved under accelerated approval based on overall response rate
• Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials

Urothelial carcinoma

• Indication for urothelial carcinoma was approved under accelerated approval based on tumor response rate and duration of response
• Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials

Pediatric:

• 2.5 mg-10 mg/kg/day orally or 20-300 mg/m2/day orally divided every 6-8 hours

Physiologic Replacement

Adult:

• 0.5-0.75 mg/kg/day orally divided every 8 hours or 25-35 mg/day
• 0.25-0.35 mg/kg intramuscularly each day

Pediatric:

• 0.5-0.75 mg/kg/day orally or 20-25 mg/sq.meter/day orally divided every 8 hours