Necitumumab (Portrazza) is a recombinant human IgG1 monoclonal antibody that acts on the EGFR (epidermal growth factor receptors). It is used in the management of patients with advanced metastatic squamous cell carcinoma of the lungs in combination with cisplatin and gemcitabine.

Necitumumab (Portrazza) Uses:

• Metastatic non-small cell lung cancer (squamous):

  • It is indicated as first-line treatment of metastatic squamous non-small cell lung cancer (NSCLC) combined with gemcitabine and cisplatin
  • Limitations of use: Not recommended for non-squamous NSCLC.

Necitumumab (Portrazza) Dose in Adults

Note:

• If the patient has a previous history of grade 1 or 2 infusion reaction, premedicate with diphenhydramine (or equivalent).
• If a patient has recurrent grade 1 or 2 infusion reaction, premedicate with diphenhydramine (or equivalent), acetaminophen, and dexamethasone (or equivalent).

Necitumumab (Portrazza) Dose in the treatment of metastatic Non-small cell lung cancer (squamous):

• Intravenous: 800 mg on days 1 and 8 of each 3week treatment cycle (combined with gemcitabine and cisplatin).
• Gemcitabine and cisplatin usually used for 6 cycles, continue necitumumab until disease progression or unacceptable toxicity.

Dose in Children:

Not indicated.

Pregnancy Risk Category: N

• Nefitumumab may cross the placenta.
• It's possible for fetal harm to occur in animal reproduction studies.
• Effective contraception is recommended during therapy, and for three months following the last dose for females of reproductive age or potential.

Use of necitumumab while breastfeeding

• It is not known if it is present in breastmilk. However, IgG antibodies from humans can be detected in breastmilk.
• It is not recommended for use by lactating mothers for three months following the last necitumumab dosage.

Dose in Kidney Disease:

The manufacturer has not provided any dose adjustment in labeling.

Dose in Liver disease:

• Mild to moderate impairment:
  • The manufacturer has not provided any dose adjustment in labeling; however, based on pharmacokinetics, dosage adjustment is not likely necessary.
• Severe impairment:
  • The manufacturer has not provided any dose adjustment in labeling (not studied).

Adverse reaction percentages reported as part of a combination regimen with gemcitabine and cisplatin.

Common Side Effects of Necitumumab (Portrazza):

• Central Nervous System:

  • Headache

• Dermatologic:

  • Skin Toxicity
  • Skin Rash
  • Acneiform Eruption

• Endocrine & Metabolic:

  • Hypomagnesemia
  • Hypocalcemia
  • Hypophosphatemia
  • Hypokalemia
  • Weight Loss

• Gastrointestinal:

  • Vomiting
  • Diarrhea
  • Stomatitis

Less Common Side Effects of Necitumumab (Portrazza):

• Cardiovascular:

  • Venous Thromboembolism
  • Arterial Thromboembolism
  • Pulmonary Embolism
  • Cardiorespiratory Arrest
  • Deep Vein Thrombosis
  • Cerebrovascular Accident
  • Ischemia
  • Myocardial Infarction

• Dermatologic:

  • Acne Vulgaris
  • Paronychia
  • Pruritus
  • Xeroderma
  • Skin Fissure

• Immunologic:

  • Antibody Development

• Ophthalmic:

  • Conjunctivitis

• Respiratory:

  • Hemoptysis

• Miscellaneous:

  • Infusion Related Reaction

Contraindications to Necitumumab (Portrazza):

The manufacturer has not indicated any contraindications in the labeling.

Warnings and precautions

• Cardiopulmonary arrest: [US-Boxed Warning]

  • With the combination of gemcitabine, cisplatin and necitumumab, a small number of patients suffered sudden death (cardiopulmonary arrest).
  • With aggressive replacement, monitor your serum electrolytes, serum calcium, and serum magnesium. It should be continued for at least eight weeks following the last dose.

• Dermatologic toxicities:

  • There are many types of dermatological toxicities that can be experienced, including dry skin, rash, dry skin and dermatitis. It typically appears within the first two weeks of starting therapy. It resolves within 17 week.
  • It is possible to need treatment interruption, dose reduction or discontinuation.
  • Patients should be advised to limit sun exposure

• Hypomagnesemia: [US Boxed Warning]

  • Patients who received necitumumab and gemcitabine, together with cisplatin, were most likely to develop hypomagnesemia.
  • Monitorization recommended for hypomagnesemia and hypocalcemia before, during and 8 weeks following treatment.
  • Nefitumumab should be withheld in the event of electrolyte abnormalities.
  • Necitumumab can be continued if hypomagnesemia or related electrolyte abnormalities are improved to grade 2 (or lower).
  • Hypomagnesemia is usually diagnosed 6 weeks after treatment begins.

• Infusion reactions

  • It has been reported that it can cause infusion-related reactions.
  • If the patient has a history of such reactions, premedicate them to prevent any further reactions.
  • Monitor for any signs or symptoms of an infusion reaction.
  • If the patient experiences any symptoms related to infusion-related drug reactions, discontinue treatment immediately.

• Thromboembolism

  • Nevitumumab was used to treat thromboembolic events, both venous or arterial. It included grades 3 and 4, as well as some fatalities. Older people are more likely to experience these events: >70 years.
  • The two most common forms of venous embolism are thrombosis in the deep veins or pulmonary emboli.
  • Most common forms of arterial thromboembolism are cerebral stroke, ischemia, and myocardial injury.
  • Stop using it if you have a life-threatening VTE/ATE

• NSCLC for non-squamous:

  • Nonsquamous NSCLC not recommended
  • Combining pemetrexed with cisplatin to treat nonsquamous NSCLC resulted in severe and fatal toxicities, cardiopulmonary arrest/sudden deaths within 30 days after the last dose.

Monitoring parameters:

• Serum electrolytes, including magnesium, potassium, and calcium (before starting the therapy, during treatment, and for at least 8 weeks following completion).
• Monitor for signs and symptoms of infusion-related reactions, dermatologic toxicity, and thromboembolism.

How to administer Necitumumab (Portrazza)?

IV:

• Administer over 60 minutes with infusion pump. through a separate line.
• Flush with sodium chloride 0.9% at the end of infusion.
• Do not infuse with other medications or with electrolytes.
• Monitor for infusion reactions;
• Reduce infusion rate by 50% for grade 1 infusion reaction; interrupt infusion for grade 2 infusion reaction.

Necitumumab should be given before gemcitabine and cisplatin.

Mechanism of action of Necitumumab (Portrazza):

• Necitumumab (epidermal growth factor receptor inhibitor) is a drug that blocks the epidermal growth factors receptor (EGFR). 
• It is a recombinant human IgG1 monoclonal anti-EGFR antibody. It binds (with a high affinity to the ligand binding site of the EGFR receptor) and inhibits receptor activation.

Half-life elimination:

• ~14 days.

Excretion:

• Clearance (mean): 14.1 mL/hour.

International Brand Names of Necitumumab:

• Portrazza

Necitumumab Brand Names in Pakistan:

No Brands Available in Pakistan.