Necitumumab is a fully human IgG1 monoclonal antibody that targets the epidermal growth factor receptor (EGFR). As of my last update in September 2021, it has been approved for the treatment of squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy. The approval was based on a clinical trial that demonstrated an improvement in overall survival when necitumumab was added to chemotherapy compared to chemotherapy alone.

EGFR is a protein present on the surface of many cells and is involved in cell growth and proliferation. Overexpression or mutations in EGFR can result in uncontrolled cell growth, leading to cancer. By targeting EGFR, necitumumab inhibits the signaling pathways that promote tumor cell growth and survival.

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 a patient had a mild or moderate bad reaction from the medicine infusion before, give them a drug like diphenhydramine before giving them the medicine again.
• If the bad reaction happens again, give them diphenhydramine, acetaminophen, and dexamethasone (or similar drugs) before giving the medicine another time.

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

• For treating a type of lung cancer that has spread, called "metastatic squamous non-small cell lung cancer", the medicine called Necitumumab is given through an IV (drip).
• The dose is 800 mg on the first day and again on the eighth day, and this is repeated every 3 weeks.
• This medicine is given alongside two other drugs, gemcitabine and cisplatin.
• In the study mentioned, patients took gemcitabine and cisplatin for up to 6 rounds (cycles).
• If the cancer didn't get worse, they continued taking only Necitumumab, even after they stopped the other two drugs.

Dose in Children:

Not indicated.

Pregnancy Risk Category: N

• Necitumumab might pass to the baby if a pregnant woman takes it.
• Based on how the drug works and tests on animals, if a baby in the womb is exposed to this drug, it might be harmed.
• So, women who can become pregnant should use reliable birth control methods while taking this medicine and continue for 3 months after the last dose.

Use of necitumumab while breastfeeding

• We don't know if necitumumab is found in breast milk.
• But similar substances can be found in it.
• Because of possible serious side effects for the baby, the company that makes the drug suggests moms don't breastfeed while taking it and for 3 months after the last dose.

Dose in Kidney Disease:

• The company that makes the drug doesn't give any guidelines about changing the dose.
• But based on how the body processes the drug, it's probably not needed to change the dose.

Dose in Liver disease:

• For people with mild to moderate health issues: The company that makes the drug doesn't say to change the dose. And based on how the body handles the drug, it's probably not needed to change the dose.

• For people with serious health issues: The company doesn't give any guidelines about changing the dose because they haven't studied it in these cases.

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 company that makes the drug hasn't listed any specific reasons or conditions for which it shouldn't be used.

Warnings and precautions

Cardiopulmonary arrest: [US-Boxed Warning]

• Warning: Some people treated with necitumumab, when used with two other drugs (gemcitabine and cisplatin), had serious heart and lung problems, and a few even died.
• So, it's very important to keep a close watch on certain blood test results (like magnesium, potassium, and calcium levels) and to replace them if they're too low, both during treatment and for at least 8 weeks after the last dose.
• Some of the people who had these serious events had other health issues, like heart disease, low magnesium, lung problems, or high blood pressure.
• It's worth noting that people with recent severe heart problems, uncontrolled high blood pressure, or uncontrolled heart failure weren't included in the main study for this lung cancer treatment.

Dermatologic toxicities:

• Many people taking this drug experience skin issues.
• This can include rashes, acne-like breakouts, dry skin, itchy skin, general rashes, cracked skin, specific kinds of rashes, or redness.
• These skin problems usually start within the first two weeks of using the drug and can last up to 17 weeks from when they begin.
• These skin issues can be severe and might lead to needing to pause treatment, take a lower dose, or even stop the drug altogether.
• People taking the medicine should try to stay out of the sun as much as possible.

Hypomagnesemia: [US Boxed Warning]

• Most people who take necitumumab with gemcitabine and cisplatin end up having low magnesium levels, and it's really bad in about one-fifth of them.
• To make sure this doesn't happen, doctors need to check your magnesium, calcium, and potassium levels before giving you each dose of necitumumab while you're being treated and for at least 8 weeks after you finish the treatment.
• If your electrolyte levels drop to a dangerous level (Grade 3 or 4), they'll stop the treatment and fix your electrolyte levels.
• You can start the treatment again once your magnesium and other electrolyte levels are better, but not until they're at a Grade 2 level or lower.
• Typically, low magnesium levels show up about 6 weeks after you start treatment.

Infusion reactions

• Some people have reactions when getting necitumumab, usually during the first or second time they get it.
• In the lung cancer study, they didn't usually give medication to prevent these reactions before the first dose.
• If someone starts showing signs of a reaction while getting the medicine, watch them closely.
• If the reaction is very serious or could be life-threatening, stop giving them the medicine.

Thromboembolism

• Some people taking necitumumab had blood clots in both veins and arteries, including severe cases and even some deaths.
• The most common clots in veins were in deep veins and in the lungs, and in arteries, they were in the brain or related to heart attacks.
• If someone has a serious or potentially deadly blood clot, stop using necitumumab.
• People who are 70 years old or older might have a higher risk of getting these clots compared to younger people.

NSCLC for non-squamous:

• Necitumumab isn't meant for people with a type of lung cancer called non-squamous NSCLC.
• In a study where necitumumab was given with two other drugs (pemetrexed and cisplatin) to treat this kind of cancer, patients faced more severe side effects and sudden deaths compared to those who only took pemetrexed and cisplatin without necitumumab.

Monitoring parameters:

Serum Electrolytes:

• Check magnesium, potassium, and calcium before each dose.
• Continue these checks for at least 8 weeks after finishing treatment.

Infusion Reactions:

• Watch for signs or symptoms during the drug infusion.

Skin Issues (Dermatologic Toxicity):

• Look out for skin problems like rashes or redness.

Blood Clots (Thromboembolism):

• Be alert for symptoms of blood clots.

How to administer Necitumumab (Portrazza)?

Duration:

• Give over 1 hour using a special pump.

Separation:

• Use a separate line for this drug.
• Once done, clear the line using a 0.9% salt solution.

Things to Avoid:

• Don't mix with other drugs or with electrolytes.

Reactions:

• Watch closely for any reactions during the infusion.
• If there's a mild reaction (grade 1): Slow down the infusion, giving it at half the speed.
• For a moderate reaction (grade 2): Stop the infusion.

Order of Drugs:

• Give Necitumumab before gemcitabine and cisplatin.

Mechanism of action of Necitumumab (Portrazza):

• Necitumumab is a special human-made antibody.
• It sticks really well to a part of a protein called EGFR, which is on the surface of some cells.
• By sticking to EGFR, it stops it from turning on and sending signals inside the cell, which is important in cancer.

Distribution:

• The drug spreads out in about 7 liters of body fluid.

How Long it Lasts:

• The amount of the drug in the body is cut in half every 14 days.

Removal:

• The body clears about 14.1 mL of the drug each hour.

International Brand Names of Necitumumab:

• Portrazza

Necitumumab Brand Names in Pakistan:

Not available.