General Information

Vectibix is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). Overexpression of EGFR is detected in many human cancers, including those of the colon and rectum. When Vectibix binds to EGFR it competitively inhibits the binding of ligands for EGFR. This results in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production.

Vectibix is specifically indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin- and irinotecan- containing chemotherapy regimens.

Mechanism of Action

Vectibix binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR.

Side Effects

Adverse events associated with the use of Vectibix may include, but are not limited to, the following:

• dermatological toxicities
• ocular toxicities
• hypomagnesemia
• fatigue
• abdominal pain
• nausea
• diarrhea
• constipation

In addition, Vectibix was shown to cause skin, ocular and mucosal related toxicities in 90 percent of patients receiving Vectibix. Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death and abscesses requiring incisions and drainage were reported. It is recommended that patients wear sunscreen and hats and limit sun exposure while receiving Vectibix since sunlight can exacerbate any skin reactions that may occur.

Dosing/Administration

Vectibix is supplied as a sterile, colorless, preservative-free solution containing 20 mg/mL designed for intravenous infusion. The recommended initial dose of the drug is 6 mg/kg administered over 60 minutes as an intravenous infusion every 14 days. If safety or tolerability concerns arise, dosage may be reduced by 50 percent. Doses higher than 1000 mg should be infused over 90 minutes.

Clinical Trial Results

FDA approval of Vectibix was based on the results of one clinical trial. This open-label, multinational, randomized, controlled trial enrolled 463 subjects with EGFR-expressing, metastatic carcinoma of the colon or rectum (mCRC). Subjects were randomized to receive Vectibix at a dose of 6 mg/kg given once every two weeks plus best supportive care (BSC) (n = 231) or BSC alone (n = 232) until disease progression. Statistical significance was seen in prolongation of progression free survival for the subjects treated with Vectibix versus those treated with BSC alone, with a mean of 96 days versus 60 days, respectively.