panitumumab (Vectibix)

Dosing and uses of Vectibix (panitumumab)

• Adult
• Pediatric

 

Adult dosage forms and strengths

injectable solution

• 20mg/mL (100mg/vial)
• 20mg/mL (200mg/vial)
• 20mg/mL (400mg/vial)

 

Colorectal Carcinoma

Indicated for wild-type KRAS (exon 2 in codons 12 or 13) metastatic colororectal carcinoma (mCRC) as determined by an FDA-approved test for this use (eg, therascreen KRAS RGQ PCR Kit)

6 mg/kg IV infusion over 60 minutes (over 90 minutes if dose >1 g) q14Days

Indications for monotherapy and combination

• Combination, first-line therapy: Indicated in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC
• Monotherapy following disease progression: Indicated as monotherapy for the treatment of EGFR-expressing mCRC in patients with disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy

Limitation of use

• Not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown
• Prior to treatment initiation, assess RAS mutational status in colorectal tumors and confirm the absence of a RAS mutation

 

Dosage modifications

Infusion Reactions: Mild-moderate (grade 1-2) reduce rate by 50%; Severe (grade 3-4) permanently discontinue

Dermatologic reactions

• First occurrence of grade 3 dermatologic reaction: Withhold 1 to 2 doses; if reaction improves to <grade 3, reinitiate at the original dose
• Second occurrence of grade 3 dermatologic reaction: Withhold 1 to 2 doses; if reaction improves to <grade 3, reinitiate at 80% of the original dose
• Third occurrence of grade 3 dermatologic reaction: Withhold 1 to 2 doses; if reaction improves to <grade 3, reinitiate at 60% of the original dose
• Fourth occurrence of grade 3 dermatologic reaction: Permanently discontinue
• Grade 3 or 4 dermatologic reaction that does not recover to <grade 3: Permanently discontinue

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Vectibix (panitumumab) adverse (side) effects

>10%

Erythema (65%)

Acneiform dermatitis (57%)

Pruritus (57%)

Hypomagnesemia (39%)

Fatigue (26%)

Abdominal pain (25%)

Paronychia (25%)

Skin exfoliation (25%)

Nausea (23%)

Rash (22%)

Constipation (21%)

Diarrhea (21%)

Vomiting (21%)

Skin fissures (20%)

Cough (14%)

Dermatologic toxicity, Grade 3 and 4 (14% )

Acne (13%)

Peripheral edema (12%)

 

1-10%

Abdominal pain, Grade 3 and 4 (7% )

Pulmonary embolism, Grades 3 to 5 (7% )

Hypomagnesemia, Grade 3 and 4 (4% )

Angioedema, All grades (3% to 4% )

Complication of infusion, All grades (3% to 4% )

Constipation, Grade 3 and 4 (3% )

Binding antibodies (0.4-3.8%)

Diarrhea, Grade 3 and 4 (2% )

Vomiting, Grade 3 and 4 (2% )

Nausea, Grade 3 and 4 (1% )

Anaphylaxis (1% )

Complication of infusion, Grade 3 and 4 (1% )

Sepsis (1%)

 

<1%

Pulmonary fibrosis

 

Frequency not defined

Conjunctivitis

Growth of eyelashes

Increased tears

Ocular hyperemia

Mucositis

Stomatitis

 

Postmarketing Reports

Skin and subcutaneous tissue disorders: Skin necrosis, angioedema

Immune system disorders: Anaphylactoid reaction

Eye disorders: Keratitis/ulcerative keratitis

Life threatening and fatal bullous mucocutaneous disease

 

Warnings

Black box warnings

Dermatologic toxicity

• Dermatologic toxicities, some severe (NCI-CTC grade 3 or higher), related to panitumumab blockade of EGF binding and subsequent inhibition of EGFR-mediated signaling pathways have been reported in patients receiving panitumumab monotherapy
• Dermatologic toxicities were reported in 90% of patients and were severe in 15% of patients receiving monotherapy
• Clinical manifestations included, but were not limited to, dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures
• Severe dermatologic toxicities were complicated by infection including sepsis, septic death, and abscesses requiring incisions and drainage
• It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (eg, Stevens Johnson syndrome or toxic epidermal necrolysis)
• Withhold or discontinue panitumumab and monitor for inflammatory or infectious sequelae in patients with severe dermatologic toxicities

 

Contraindications

None

 

Cautions

Increased tumor progression, increased mortality, or lack of benefit in patients with RAS-mutant mCRC; determine RAS-mutant tumor status in an experienced laboratory using an FDA-approved test before treatment

Monitor patients who develop dermatologic toxicities while receiving panitumumab for the development of inflammatory or infectious sequelae; limit sun exposure

Panitumumab is not indicated for use in combination with chemotherapy due to increase in mortality or toxicity

Permanently discontinue in patients developing pulmonary fibrosis/interstitial lung disease

Monitor for keratitis or ulcerative keratitis; interrupt or discontinue panitumumab for acute or worsening keratitis

Monitor electrolytes and institute appropriate treatment if needed

Terminate the infusion for severe infusion reactions

Ocular toxicities reported; monitor for keratitis or ulcerative keratitis; interrupt or discontinue for acute or worsening keratitis

Discontinue permanently if patient develops interstitial lung disease, pneumonitis, or lung infiltrates

Avoid pregnancy

 

Pregnancy and lactation

Pregnancy category: C

Lactation: not known if excreted in breast milk, do not nurse during & for at least 2 mth post-treatment

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Vectibix (panitumumab)

Mechanism of action

Human monoclonal antibody to human EGF receptor

 

Pharmacokinetics

Peak Plasma Concentration: 213±59 mcg/mL

Trough Concentration: 39±14 mcg/mL

Half-Life, Elimination: 7.5 days

Clearance: 4.9±1.4 mL/kg/day

 

Pharmacogenomics

Colorectal cancer expressing with KRAS wild-type respond more favorably to regimens that include anti-EGFR antibodies (cetuximab, panitumumab); whereas, the presence of KRAS mutation (codon 12 or 13) showed an absence of biological and clinical activity for the anti-EGFR antibody treatment

Strongly recommended that patients with metastatic CRC who are being considered for treatment with anti-EGFR antibody therapy should be tested for the presence of a KRAS mutation prior to the administration of therapy (NCCN guidelines)

Genetic testing laboratories

• The following companies are currently offering KRAS mutation status testing
• Clarient, Inc. (https://www.clarientinc.com)
• Caris Diagnostics (https://www.carisdx.com)
• DxS (https://www.dxsdiagnostics.com)
• Genzyme Genetics (https://www.genzymegenetics.com)
• LabCorp (https://www.labcorp.com)
• Response Genetics (https://www.responsegenetics.com)

 

Administration

IV Preparation

Inspect vial; discard if discolored

Some particulate matter may be present, OK to use (will be removed by filter)

Withdraw dose amount & dilute to 100 mL with 0.9% NaCl (if dose >1 g, in 150 mL)

Mix by gentle inversion, do not shake

Final concentration not to exceed 10 mg/mL

Use diluted solution within 6 hr if stored at room temp, or within 24 hr if stored at 2-8°C

 

IV Administration

Use low-protein-binding 0.2-0.22 micron in-line filter

Flush IV line with 0.9% NaCl before and after administration

Use infusion pump

Infuse over 60 min ( 90 min if dose >1 g) through peripheral line or indwelling catheter