Panitumumab (Vectibix) is a fully human IgG2 monoclonal antibody that targets the EGFR (epidermal growth factor receptors).

Panitumumab Uses:

• Metastatic Colorectal Cancer:

  • Treatment of wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an approved test) metastatic colorectal carcinoma (mCRC), either as first-line therapy in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or as a single agent therapy following disease progression after earlier treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy

• Limitations of use:

  • Panitumumab is not indicated for the treatment of patients with RAS-mutant metastatic colorectal carcinoma (mCRC) or for whom RAS mutation status is unknown.

• Off Label Use of Panitumumab in Adults:

  • metastatic colorectal cancer, KRAS wild-type (in combination with other chemotherapy agents)

Panitumumab Dose in Adults

• Note: Establish RAS mutation status (to confirm RAS wild-type) before treatment initiation.

Panitumumab Dose in the treatment of metastatic colorectal cancer, RAS wild-type:

• 6 mg/kg IV every 2 weeks as a single agent or in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin);
• continue until disease progression or unacceptable toxicity.

Panitumumab Dose in the treatment of metastatic colorectal cancer, RAS wild-type in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan; off-label combination):

• IV: 6 mg/kg every 2 weeks;
• continue until disease progression or unacceptable toxicity.

Use in children:

The safety and efficacy of the drug in children have not been established.

Panitumumab Pregnancy Risk Category: C

• Based on animal reproduction studies and the mechanism of action, panitumumab can cause harm to fetal health if administered during pregnancy.
• Panitumumab (humanized monoclonal antibody, IgG) is a panitumumab.
• The IgG subclass and gestational year are important factors in placental transfer. It generally increases with pregnancy progression.
• During the organogenesis period, you would expect to be exposed at a minimum.
• Panitumumab causes inhibition of epidermal Growth Factor (EGF), which is a component in fetal development. Therefore, it would be reasonable to expect adverse effects on pregnancy.
• Effective contraception should be used by females with reproductive potential during treatment, and at least for 2 months after the last dose.

Use panitumumab while breastfeeding

• It is unknown if panitumumab can be found in breast milk.
• Panitumumab, an IgG monoclonal antibody, and maternal IgG immunoglobulins can be excreted from breast milk.
• However, it is not likely that breast milk antibodies will enter infant and neonatal circulation in large quantities.
• The manufacturer suggests that women refrain from breastfeeding during therapy or for at least 2 months after receiving the last panitumumab dose.

Panitumumab Dose in Kidney Disease:

• There are no dosage adjustments provided in the drug manufacturer's labeling (has not been studied).

Panitumumab Dose in Liver Disease:

• There are no dosage adjustments provided in the drug manufacturer's labeling (has not been studied).

Monotherapy:

Common Side Effects of Panitumumab (Vectibix):

• Central Nervous System:

  • Fatigue

• Dermatologic:

  • Skin Toxicity
  • Erythema
  • Pruritus
  • Acneiform Eruption
  • Paronychia
  • Rash
  • Skin Fissure
  • Exfoliative Dermatitis
  • Acne Vulgaris

• Endocrine & Metabolic:

  • Hypomagnesemia

• Gastrointestinal:

  • Nausea
  • Diarrhea
  • Vomiting

• Ophthalmic:

  • Ocular Toxicity

• Respiratory:

  • Dyspnea
  • Cough

• Miscellaneous:

  • Fever

Less Common Side Effects Of Panitumumab (Vectibix):

• Cardiovascular:

  • Pulmonary Embolism

• Central Nervous System:

  • Chills

• Dermatologic:

  • Nail Toxicity
  • Xeroderma
  • Desquamation
  • Dermal Ulcer
  • Pustular Rash
  • Papular Rash

• Endocrine & Metabolic:

  • Dehydration

• Gastrointestinal:

  • Mucositis
  • Stomatitis
  • Xerostomia

• Immunologic:

  • Antibody Formation

• Ophthalmic:

  • Abnormal Eyelash Growth
  • Conjunctivitis

• Respiratory:

  • Epistaxis
  • Interstitial Pulmonary Disease

• Miscellaneous:

  • Infusion Related Reaction

Combination Therapy With FOLFOX:

Common Side Effects Of Panitumumab (Vectibix):

• Dermatologic:

  • Skin Rash
  • Acneiform Eruption
  • Pruritus
  • Paronychia
  • Xeroderma
  • Erythema
  • Skin Fissure
  • Alopecia
  • Acne Vulgaris

• Endocrine & Metabolic:

  • Hypomagnesemia
  • Hypokalemia
  • Weight Loss

• Gastrointestinal:

  • Diarrhea
  • Anorexia
  • Abdominal Pain
  • Stomatitis
  • Mucosal Inflammation

• Neuromuscular & Skeletal:

  • Weakness

• Ophthalmic:

  • Conjunctivitis

• Respiratory:

  • Epistaxis

Less Common Side Effects Of Panitumumab (Vectibix):

• Cardiovascular:

  • Deep Vein Thrombosis

• Central Nervous System:

  • Fatigue
  • Paresthesia

• Dermatologic:

  • Nail Disorder
  • Palmar-Plantar Erythrodysesthesia
  • Cellulitis

• Endocrine & Metabolic:

  • Dehydration
  • Hypocalcemia

• Hypersensitivity:

  • Hypersensitivity

• Local:

  • Localized Infection

Contraindications to Panitumumab (Vectibix):

• The US labeling of the manufacturer does not list any contraindications.
• Canadian labeling
  • Previous history of life-threatening or severe hypersensitivity reactions to panitumumab and any component of the formulation

Warnings and precautions

• Dermatologic toxicities: [US Boxed Warning]

  • Patients who received single drug panitumumab have had skin toxicities reported in 90%. Severe skin reactions (grade 3 or greater) were also observed in 15% of patients. These included dermatitis, erythema and pruritus.
  • Infection, sepsis and necrotizing fasciitis can all lead to severe skin toxicities.
  • The median time for skin (or ocular toxicities) was 14 days. There was resolution within 12 weeks.
  • A response is predetermined based on the severity of toxic effects.
  • Toxicities in grades 2 through 4 are associated with better survival rates and overall survival than those in grade 1.
  • For the prevention of infection or inflammation, monitor all dermatologic toxicities.
  • Rare cases of Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis have been reported. Bullous mucocutaneous diseases (life-threatening/fatal) have also been reported.
  • You should not receive treatment for severe or life-threatening skin or soft tissue toxicities that are associated with serious/life-threatening inflammatory and infectious complications.
  • Dermatological toxicity can require dose reductions or discontinuation.
  • Sunlight exposure should be avoided. Wear sunscreen and protective clothing/hats.
  • It has also been reported that nails can be toxic.

• Diarrhea

  • Combination chemotherapy can cause diarrhea.
  • Combination chemotherapy with panitumumab has been associated with severe diarrhea and dehydration.
  • It has also been reported that gastric mucosal toxicities have occurred.

• Depletion of electrolytes:

  • Treatment may cause magnesium and/or calcium depletion (may be delayed; hypomagnesemia occurred more than 2 months after the completion of panitumumab). After treatment has ended, electrolyte replacement may be necessary.
  • Monitor for hypomagnesemia or hypocalcemia throughout treatment, and at least for 2 months after it is completed.
  • It has also been reported that hypokalemia is a possibility.

• Infusion reactions

  • Infusion reactions that are severe (bronchospasm and dyspnea, fevers, chills, hypotension, or fever) have been reported in less than 1% of patients. Postmarketing surveillance has been used to monitor fatal infusion reactions.
  • Stop infusions for severe reactions. If patients have persistent severe reactions, discontinue infusions permanently.
  • It is important to have immediate access to appropriate medical assistance for infusion reactions.
  • You can manage mild to moderate infusion reactions by slowing down the infusion rate.

• Ocular toxicities:

  • Keratitis, ulcerative keratitis, and other risk factors have been reported.
  • You should monitor for ocular toxicities and stop or suspend treatment for severe or more severe keratitis.

• Toxicity in the lungs:

  • Clinical trials have not shown a lot of evidence for pulmonary fibrosis or interstitial lung disease. There have been fatalities.
  • If symptoms worsen or become acutely severe, discontinue treatment immediately. Interrupt treatment if interstitial lung disease has been confirmed.
  • Most clinical trials were canceled for patients with interstitial pneumonia or pulmonary Fibrosis.
  • Take into account the risks and benefits of treatment for patients with pulmonary complications.

• Status of RAS mutation and colorectal cancer:

  • Before you start treatment, confirm that there is no RAS mutation.
  • Patients with codons 12-13 (exon 2), codons 59-61 (exon 3) or codons 117-146 (exon 4) RAS or NRAS mutations are less likely to receive EGFR inhibitor therapy.
  • Patients with RAS mutation-positive metastatic cancer and patients with unknown RAS mutation status are not recommended.
  • Patients with RAS mutations were treated with an anti-EGFR directed antibody. This increased toxicity was not clinically significant.
  • Patients with KRAS mutations who received panitumumab with FOLFOX4 had a significantly lower chance of surviving.
  • A subset of KRAS patients with wild-type KRAS also showed additional RAS (KRAS [exons 3, 4,] or NRAS[exons 2, 3, 4,]) mutations.
  • Patients with RAS mutations were significantly less likely to survive if they received FOLFOX4 and panitumumab together.
  • According to the American Society of Clinical Oncology's provisional clinical opinion update, all patients with metastatic colorectal carcinoma should be tested in a certified laboratory for mutations or changes in KRAS and NRAS exons 2 and 3 (codons 59-61), exon 3 and exon 3, respectively, and exon 4 (codons 117-146). Anti-EGFR monoclonal anti-EGFR therapy should only be recommended for patients whose tumors have not been confirmed by extended RAS testing.
  • Information about tests that can detect RAS mutations is available at www.fda.gov/CompanionDiagnostics.
  • Panitumumab has also been shown to not be effective in patients with the BRAF V600E mutation.

Panitumumab: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

• Before treatment can begin, it is important to perform RAS genotyping on tumor tissue in order to determine RAS mutation status.
• Monitor serum electrolytes including magnesium, calcium, and potassium (periodically during therapy and for at most 8 weeks thereafter).
• Monitor your vital signs and temperature prior to, during, or after infusion.
• For signs of ocular toxicities, skin toxicity and acute onset/worsening of pulmonary symptoms, monitor closely.

How to administer Panitumumab (Vectibix)?

• Only for IV infusion; don't administer as an IV push, or as a Bolus.
• Use an infusion pump to infuse through a low-protein-binding, 0.22-micrometer inline filter.
• Doses below 1,000 mg should be infused for at least one hour. If the first dose is well tolerated, additional doses can be given over half an hour.
• Doses >1,000mg, infuse for more than 90 minutes
• Infusion: Flush line with NS before and after infusion
• Do not combine or give other medications.
• Reduce infusion rate by half if you have mild to moderate reactions, i.e. grades 1 and 2. Stop infusion if you experience severe infusion reactions (i.e. grades 3 and 4.) and consider discontinuing the drug permanently.
• It is important to have access to the appropriate medical assistance for infusion reactions.

Mechanism of action of Panitumumab (Vectibix):

• It is a recombinant human IgG2 monoclonal anti-mouse antibody. It binds specifically to the epidermal Growth Factor receptor (EGFR, HER1, c–ErbB-1) and causes competitive inhibition in the binding of epidermal Growth Factor (EGF).
• The EGFR binding blocks phosphorylation/activation of intracellular tyrosine kinases. This results in cell death, growth, proliferation and transformation.
• EGFR signal transduction could result in KRAS or NRAS wild type activation. Cells with RAS mutations seem to not be affected by EGFR inhibition.

Half-life elimination:

• ~7.5 days (range: 4 to 11 days)

International Brands of Panitumumab:

• Vectibix

Panitumumab Brand Names in Pakistan:

No Brands Available in Pakistan.