Portrazza

Necitumumab instruction manual

Common name: Necitumumab

Trade name: Portrazza

Full names: Necitumumab, Portrazza , necitumumab

Indications:

PORTRAZZA™ is an epidermal growth factor receptor (EGFR) antagonist suitable for use in combination with gemcitabine and cisplatin for the first-line treatment of patients with metastatic squamous non-small cell lung cancer.

Restrictions on Use: PORTRAZZA is not indicated for the treatment of non-squamous non-small cell lung cancer.

Usage and dosage:

(1) The recommended dose of Necitumumab is 800 mg (absolute dose);

(2) One course of treatment every three weeks, with intravenous infusion over 60 minutes on days 1 and 8;

(3) Use before gemcitabine and cisplatin;

(4) Until disease progression or unacceptable toxicity.

Dose adjustments should be made if an infusion-related reaction (IRR) occurs with Necitumumab:

(1) For grade 1 IRR, reduce the infusion rate of Necitumumab by 50%.

(2) For Grade 2 IRR, withhold infusion until signs and symptoms have resolved to Grade 0 or 1; resume necitumumab at 50% reduced rate for all subsequent infusions.

(3) Permanently discontinue necitumumab for grade 3 or 4 IRR.

Strength:

800mg/50mL

Adverse Reactions:

The most common adverse reactions (all grades) observed in PORTRAZZA-treated patients at an incidence of ≥30% and ≥2% higher than in the gemcitabine and cisplatin alone arm were rash and hypomagnesemia.

Symptoms such as acne, dryness, diarrhea, vomiting, mouth sores, vision changes, red, watery or itchy eyes, red and swollen nails, and itching may also occur.

Contraindications:

None

Precautions:

Cardiorespiratory arrest: Monitor serum electrolytes closely during and after PORTRAZZA.

Hypomagnesemia: Monitor for at least 8 weeks before and after each infusion of PORTRAZZA. PORTRAZZA should not be administered for Grade 3 or 4 electrolyte abnormalities; subsequent courses of PORTRAZZA may be given in these patients once the electrolyte abnormalities have improved to ≤Grade 2. Replenish electrolytes if necessary.

Venous and arterial thrombotic events (VTE and ATE): Discontinue PORTRAZZA for severe VTE or ATE.

Dermatologic Toxicity: Monitor for dermatologic toxicity and withhold or discontinue PORTRAZZA for severe toxicity. Limit sun exposure.

Infusion-Related Reactions: Monitor for signs and symptoms during and after the infusion. Discontinue PORTRAZZA for severe reactions.

Increased toxicity: Non-squamous NSCLC - increased toxicity and increased mortality.

Embryo-fetal toxicity: May cause fetal harm. Advise women of reproductive potential of the potential risks to the fetus and to use effective contraception.

Storage:

Store vials in refrigerator at 2° to 8°C (36° to 46°F) until use. Store vials in external carton for protection from light. Do not freeze or shake vial.

Mechanism of action:

Necitumumab is a recombinant human IgG1 monoclonal antibody that binds to human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands. EGFR expression and activation have been associated with malignant progression, induction of angiogenesis, and inhibition of apoptosis. Necitumumab binding induces EGFR internalization and degradation in vitro. In vitro, binding of necitumumab also results in antibody-dependent cellular cytotoxicity (ADCC) in EGFR-expressing cells.

In in vivo studies using xenograft models of human cancers, including non-small cell lung cancer, administration of necitumumab to transplanted mice resulted in increased antitumor activity in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone.

Safety and efficacy:

Portrazza’s approval is based on the first and only randomized phase III study conducted specifically in metastatic squamous lung cancer. According to study data, compared with the control group, the Portrazza combination treatment group had a better overall survival (median OS: 11.5 months). vs 9.9 months, p=0.01), progression-free survival (median PFS: 5.7 months vs 5.5 months, p=0.02), while reducing the risk of death by 16%.