Vectibix Special Precautions

Dermatologic and soft tissue toxicity: Skin and subcutaneous tissue disorders, a pharmacologic effect observed with epidermal growth factor receptor (EGFR) inhibitors, were frequently reported [approximately 93% in patients across the monotherapy mCRC clinical trials (n = 1,052)].
It is recommended that patients wear sunscreen and hats and limit sun exposure while receiving VECTIBIX as sunlight can exacerbate any skin reactions that may occur.
For dose modifications related to dermatological toxicity, see DOSE MODIFICATIONS - DERMATOLOGIC TOXICITY under Dosage & Administration.
Patients who develop dermatologic or soft tissue toxicities while receiving VECTIBIX should be monitored for the development of inflammatory or infectious sequelae.
Life-threatening and fatal infectious complications including events of necrotising fasciitis and/or sepsis have been observed in patients treated with VECTIBIX.
Rare cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients treated with VECTIBIX in the postmarketing setting.
Stop or discontinue VECTIBIX for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications.
Eye toxicity: Serious cases of keratitis, ulcerative keratitis, and corneal perforation have been reported. Patients who develop eye toxicities while receiving VECTIBIX should be monitored for evidence of keratitis, ulcerative keratitis, or corneal perforation.
Infusion reactions: Infusion reactions, including anaphylactic reactions, bronchospasm, and hypotension, have been reported in clinical trials and postmarketing experience. Across the monotherapy mCRC clinical trials (n = 1,052), severe infusion reactions (NCI-CTC grade 3 and grade 4) occurred with the administration of VECTIBIX in 0.5% of patients.
In the (pooled) irinotecan-based chemotherapy with VECTIBIX (n = 951) and the irinotecan-based chemotherapy alone (n = 594) settings, severe infusion reactions (NCI-CTC grade 3 and grade 4) occurred in 0.1% and 0.2% of patients, respectively. In the oxaliplatin-based chemotherapy with VECTIBIX (n = 585) and the oxaliplatin-based chemotherapy alone (n = 584) settings, severe infusion reactions (NCI-CTC grade 3 and grade 4) occurred in 2.4% of patients in both treatment arms.
Stop infusion if a severe or life-threatening infusion reaction occurs. Depending on the severity and/or persistence of the reaction, consider permanently discontinuing VECTIBIX.
Other hypersensitivity reactions: Hypersensitivity reactions have been reported, including a fatal case of angioedema that occurred more than 24 hours after the infusion. Depending on the severity (e.g., presence of bronchospasm, edema, angioedema, hypotension, need for parenteral medication, or anaphylaxis) and/or persistence, of the hypersensitivity reactions; permanently discontinue VECTIBIX (see Contraindications and Adverse Reactions).
Pulmonary toxicity: Fatal and non-fatal cases of interstitial lung disease (ILD) have been observed in patients treated with EGFR inhibitors including VECTIBIX. In the event of acute onset or worsening of pulmonary symptoms, VECTIBIX therapy should be interrupted and a prompt investigation of these symptoms should occur. If ILD is confirmed, VECTIBIX should be permanently discontinued and the patient should be treated appropriately.
In patients with a history of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with VECTIBIX versus the risk of pulmonary complications must be carefully considered.
VECTIBIX in combination with irinotecan, bolus 5-fluorouracil, and leucovorin (IFL) chemotherapy: In a single-arm study (n = 19), patients receiving VECTIBIX in combination with irinotecan, bolus 5-fluorouracil, and leucovorin administered as the IFL regimen experienced a high incidence of severe diarrhea (58%), therefore, administration of VECTIBIX in combination with IFL should be avoided.
VECTIBIX in combination with bevacizumab and oxaliplatin-containing chemotherapeutic regimens or VECTIBIX in combination with bevacizumab and irinotecan-containing chemotherapeutic regimens for first-line treatment of metastatic colorectal cancer: A randomized, open-label, multicenter study of 1,053 patients evaluated the efficacy and safety of bevacizumab and oxaliplatin- or irinotecan-containing chemotherapeutic regimens with and without VECTIBIX in the first-line treatment of metastatic colorectal cancer.
Across both chemotherapy treatment groups, more toxicity was seen in the VECTIBIX group, manifesting as a greater incidence of grade 3 and higher adverse events, a greater incidence of serious adverse events, and more overall deaths relative to the control group. Similar safety trends were seen for the oxaliplatin and irinotecan treatment groups separately.
Serious adverse events were experienced by 59% in the VECTIBIX group versus 37% in the control group, with higher incidences in the VECTIBIX group of dehydration, diarrhea, pulmonary embolism, nausea, and vomiting. Serious infections overall displayed a treatment difference (15% versus 9%); however, no one specific type of infection occurred at a high frequency. Nineteen percent of patients receiving VECTIBIX experienced a serious event that was considered related to VECTIBIX, the most common of which were diarrhea, dehydration, and vomiting.
This study did not demonstrate an improvement in progression-free survival (the primary endpoint) by the addition of VECTIBIX to bevacizumab and oxaliplatin-based chemotherapy. The addition of VECTIBIX to the combination of bevacizumab and chemotherapy in first-line metastatic colorectal cancer is not indicated.
VECTIBIX in combination with oxaliplatin-based chemotherapy in patients with mutant RAS mCRC or for whom RAS status is unknown: VECTIBIX should not be administered in combination with oxaliplatin-containing chemotherapy to patients with mutant RAS mCRC or for whom RAS status is unknown (see Contraindications).
In the primary analysis of a phase 3 study (n = 1,183; 656 patients with wild-type KRAS (exon 2) and 440 patients with mutant KRAS mCRC) evaluating VECTIBIX in combination with infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) compared with FOLFOX alone as first-line therapy for mCRC, a significant shortening of progression-free survival (PFS) was observed in patients with mutant KRAS mCRC who received VECTIBIX and FOLFOX (n = 221) versus FOLFOX alone (n = 219). A trend toward shortened overall survival (OS) time was also observed in the mutant KRAS mCRC population.
A predefined retrospective subset analysis of 641 patients of the 656 patients with wild-type KRAS (exon 2) mCRC from the phase 3 study identified additional RAS (KRAS [exons 3 and 4] or NRAS [exons 2, 3, 4]) mutations in 17% (n = 108) of patients. A shortening of PFS and OS was observed in patients with mutant RAS mCRC who received VECTIBIX and FOLFOX (n = 51) versus FOLFOX alone (n = 57) (see Laboratory tests as follows).
Acute renal failure: Acute renal failure has been observed in patients who develop severe diarrhea and dehydration.
Patients with ECOG 2 performance status treated with VECTIBIX in combination with chemotherapy: In a phase 3 study (n = 1,183; 656 patients with wild-type KRAS and 440 patients with mutant KRAS mCRC) evaluating VECTIBIX in combination with infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) compared to FOLFOX alone as first-line therapy, wild-type KRAS mCRC patients with ECOG 2 (Eastern Cooperative Oncology Group) performance status [n = 37; n = 19 (VECTIBIX plus FOLFOX), n = 18 (FOLFOX alone)] were observed to have increased toxicity and significant shortening of progression-free survival (PFS) and overall survival (OS) relative to ECOG 0 or 1 performance status (n = 611). In patients with wild-type KRAS mCRC, adverse events with > 20% difference between treatment arms within each ECOG group, and a > 5% difference between ECOG groups of the VECTIBIX plus FOLFOX arm were hypomagnesemia, hypokalemia, anemia, and weight decreased. Similar safety findings were observed in patients with wild-type RAS mCRC. For patients with ECOG 2 performance status, assessment of risk-benefit is recommended prior to initiation of VECTIBIX in combination with chemotherapy for treatment of mCRC.
Laboratory tests: Electrolyte disturbances/monitoring: Progressively decreasing serum magnesium levels leading to severe hypomagnesaemia have been observed in some patients. Patients should be monitored for hypomagnesaemia and accompanying hypocalcaemia prior to initiating VECTIBIX treatment, and periodically during VECTIBIX treatment and for up to 8 weeks after the completion of treatment. Magnesium repletion is recommended, as appropriate.
Other electrolyte disturbances, including hypokalaemia, have also been observed. Repletion of these electrolytes is also recommended, as appropriate.
Tumor genetic marker testing: Evidence of wild-type RAS (KRAS and NRAS) status is required before initiating treatment with VECTIBIX. Mutational status should be determined by an experienced laboratory using validated test methods for detection of KRAS (exons 2, 3, and 4) and NRAS (exons 2, 3, and 4) mutations (see Contraindications).
Effects on ability to drive and use machines: No studies on the effect on the ability to drive or use heavy machinery have been performed in patients receiving panitumumab. If patients experience treatment-related symptoms affecting their vision and/or ability to concentrate and react, it is recommended that they do not drive or use machines until the side effect subsides.
Use in Children: The safety and effectiveness of VECTIBIX in pediatric patients has not been established.
Use in the Elderly: No overall differences in safety or efficacy were observed in elderly patients (≥ 65 years of age) treated with VECTIBIX monotherapy. However, an increased number of serious adverse events were reported in elderly patients treated with VECTIBIX in combination with irinotecan or oxaliplatin-based chemotherapy compared to chemotherapy alone.