Important Safety Information, including Boxed WARNINGS

Vectibix^® is not indicated for use in combination with chemotherapy. In an interim analysis of a randomized clinical trial, the addition of Vectibix^® to the combination of bevacizumab and chemotherapy resulted in decreased overall survival and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix^®-treated patients included rash/dermatitis/acneiform (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%) and hypomagnesemia (4% vs 0%). NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix^®-treated patients (7% vs 4%) and included fatal events in 3 (< 1%) Vectibix^®-treated patients. 

In a single-arm study of 19 patients receiving Vectibix^® in combination with IFL, the incidence of NCI-CTC grade 3-4 diarrhea was 58%; in addition, grade 5 diarrhea occurred in 1 patient. In a single-arm study of 24 patients receiving Vectibix^® plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea was 25%.

Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix^®.  Of the 2 cases, 1 involved a patient with underlying idiopathic pulmonary fibrosis and resulted in death. The second patient had symptoms of pulmonary fibrosis, which was confirmed by CT. Additionally, a third patient died with bilateral pulmonary infiltrates of uncertain etiology with hypoxia. 

In the randomized, controlled clinical trial, median magnesium levels decreased by 0.1 mmol/L in the Vectibix^® arm; hypomagnesemia (NCI-CTC grade 3 or 4) requiring oral or IV electrolyte repletion occurred in 2% of patients.  Patients’ electrolytes should be periodically monitored during and for 8 weeks after the completion of Vectibix^® therapy.

Exposure to sunlight can exacerbate dermatologic toxicity. It is recommended that patients wear sunscreen and hats, and limit sun exposure while receiving Vectibix^®.

The most common adverse events of Vectibix^® are skin rash with variable presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea, including diarrhea resulting in dehydration. The most serious adverse events of Vectibix^® are pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, and constipation.

Indication

Vectibix^® (panitumumab) is indicated as a single agent for the treatment of epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma (mCRC) with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

The effectiveness of Vectibix^® as a single agent for the treatment of EGFR-expressing mCRC is based on progression-free survival.  Currently, no data demonstrate an improvement in disease-related symptoms or increased survival with Vectibix^®.

Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for Vectibix^® in patients whose tumors had KRAS mutations in codon 12 or 13.  Use of Vectibix^® is not recommended for the treatment of colorectal cancer with these mutations.

Important Safety Information, including Boxed WARNINGS

Vectibix^® is not indicated for use in combination with chemotherapy. In an interim analysis of a randomized clinical trial, the addition of Vectibix^® to the combination of bevacizumab and chemotherapy resulted in decreased overall survival and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix^®-treated patients included rash/dermatitis/acneiform (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%) and hypomagnesemia (4% vs 0%). NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix^®-treated patients (7% vs 4%) and included fatal events in 3 (< 1%) Vectibix^®-treated patients. 

In a single-arm study of 19 patients receiving Vectibix^® in combination with IFL, the incidence of NCI-CTC grade 3-4 diarrhea was 58%; in addition, grade 5 diarrhea occurred in 1 patient. In a single-arm study of 24 patients receiving Vectibix^® plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea was 25%.

Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix^®.  Of the 2 cases, 1 involved a patient with underlying idiopathic pulmonary fibrosis and resulted in death. The second patient had symptoms of pulmonary fibrosis, which was confirmed by CT. Additionally, a third patient died with bilateral pulmonary infiltrates of uncertain etiology with hypoxia. 

In the randomized, controlled clinical trial, median magnesium levels decreased by 0.1 mmol/L in the Vectibix^® arm; hypomagnesemia (NCI-CTC grade 3 or 4) requiring oral or IV electrolyte repletion occurred in 2% of patients.  Patients’ electrolytes should be periodically monitored during and for 8 weeks after the completion of Vectibix^® therapy.

Exposure to sunlight can exacerbate dermatologic toxicity. It is recommended that patients wear sunscreen and hats, and limit sun exposure while receiving Vectibix^®.

The most common adverse events of Vectibix^® are skin rash with variable presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea, including diarrhea resulting in dehydration. The most serious adverse events of Vectibix^® are pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, and constipation.