What is Vectibix®?
Vectibix® is a fully human anti-EGFR monoclonal antibody1
Mechanism of action
- Vectibix® is an antibody that binds with high affinity and specificity to the human EGFR, which inhibits receptor autophosphorylation induced by all known EGFR ligands1
- Binding of Vectibix® to EGFR results in:1
- Internalisation of the receptor
- Inhibition of cell growth
- Induction of apoptosis
- Decreased interleukin-8 and VEGF production
Immunogenicity
Vectibix®
- Fully human1
- Fully human antibodies decrease the risk of immunogenicity2
Chimeric monoclonal antibody
- Part mouse protein3
- The mouse protein in chimeric antibodies can trigger the formation of neutralising antibodies2
References:
- Vectibix® Summary of Product Characteristics.
- Weiner LM. J Immunother 2006;29:1-9.
- Resch G et al. Ann Oncol 2011;22:486-7.
How is Vectibix® used in patients with mCRC?
Vectibix® indications
Vectibix® is indicated for the treatment of adult patients with wild-type RAS mCRC:1
- In first-line in combination with FOLFOX or FOLFIRI
- In second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan)
- As monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens
Vectibix® contraindications
- Patients with a history of severe or life-threatening hypersensitivity to the active substance or to any of the excipients1
- Patients with interstitial pneumonitis or pulmonary fibrosis1
- Patients with mutant RAS mCRC or for whom RAS mCRC status is unknown, in combination with oxaliplatin-containing chemotherapy1
Please see the Summary of Product Characteristics for more information
References:
- Vectibix® Summary of Product Characteristics.
Vectibix® dosing and administration
Before infusion
Recommended dose for infusion
After infusion
Dilute Vectibix® in sodium chloride 9 mg/mL (0.9%). Withdraw the necessary amount of Vectibix® for a dose of 6 mg/kg. Dilute in a total volume of 100 mL1
6 mg/kg of bodyweight given once every 2 weeks1
Flush the infusion line with sodium chloride solution to avoid mixing with other medicinal products or intravenous solutions1
Flush the infusion line with sodium chloride solution to avoid mixing with other medicinal products or intravenous solutions1
Special precautions1
Do not shake or vigorously agitate the vial. Do not administer Vectibix® if discolouration is observed. The final concentration should not exceed 10 mg/mL. Doses higher than 1000 mg should be diluted in 150 mL sodium chloride 9 mg/mL (0.9%) solution for injection. The diluted solution should be mixed by gentle inversion, do not shake.
- Administer Vectibix® as an intravenous infusion via an infusion pump, using a low protein binding 0.2 or 0.22 μm in-line filter, through a peripheral line or indwelling catheter1
Recommended infusion time:1
~60
minutes
If first infusion is tolerated, then administer subsequent infusions over:1
30 to 60
minutes
Infuse doses of
>1000 mg over:1
~90
minutes
- Do not administer Vectibix® as an intravenous push or bolus1
- A reduction in the rate of infusion may be necessary in cases of infusion-related reactions1
References:
- Vectibix® Summary of Product Characteristics.
Vectibix® important safety information
The information provided on this page is a summary of adverse reactions that may be encountered with Vectibix®. For comprehensive coverage of the safety and tolerability profile of Vectibix®, please refer to the Summary of Product Characteristics.
Skin toxicity
- The most commonly reported adverse reactions are skin reactions, occurring in 93% of patients1
- Skin toxicity is a very common adverse event with drugs of the anti-EGFR monoclonal antibody class1,2
- Most skin reactions are mild to moderate in nature with 34% severe (grade 3) and <1% life-threatening (grade 4); life-threatening and fatal infectious complications have been observed in patients who received Vectibix® in combination with chemotherapy1
- Pre-emptive skin treatment reduced the incidence of grade ≥2 skin toxicities with Vectibix® by ~50%3
- If your patient experiences skin symptom(s) that are grade 3 or higher, or that are considered intolerable, the Summary of Product Characteristics recommends to adjust the Vectibix® dose1
Summary of adverse reactions
The data in the table below describe adverse reactions reported from clinical studies in patients with mCRC who received Vectibix® as a single agent or in combination with chemotherapy (n=2588) and spontaneous reporting. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
| MedDRA system organ class | Adverse reactions | ||||
|---|---|---|---|---|---|
| Very common (≥1/10) | |||||
| Infections and infestations | Paronychia | ||||
| Blood and lymphatic system disorders | Anaemia | ||||
| Immune system disorders | |||||
| Metabolism and nutrition disorders | Hypokalaemia Anorexia Hypomagnesaemia |
||||
| Psychiatric disorders | Insomnia | ||||
| Nervous system disorders | |||||
| Eye disorders | Conjunctivitis | ||||
| Cardiac disorders | |||||
| Vascular disorders | |||||
| Respiratory, thoracic and mediastinal disorders | Dyspnoea Cough |
||||
| Gastrointestinal disorders | Diarrhoea Nausea Vomiting Abdominal pain Stomatitis Constipation |
||||
| Skin and subcutaneous tissue disorders | Dermatitis acneiform Rash† Erythema Pruritus Dry skin Skin fissures Acne Alopecia |
||||
| Musculoskeletal and connective tissue disorders | Back pain | ||||
| General disorders and administration site conditions | Fatigue Pyrexia Asthenia Mucosal inflammation Oedema peripheral |
||||
| Investigations | Weight decreased | ||||
| MedDRA system organ class | Adverse reactions | ||||
|---|---|---|---|---|---|
| Common (≥1/100 to <1/10) | |||||
| Infections and infestations | Rash pustular Cellulitis Folliculitis Localised infection |
||||
| Blood and lymphatic system disorders | Leukopenia | ||||
| Immune system disorders | Hypersensitivity | ||||
| Metabolism and nutrition disorders | Hypocalcaemia Dehydration Hyperglycaemia Hypophosphataemia |
||||
| Psychiatric disorders | Anxiety | ||||
| Nervous system disorders | Headache Dizziness |
||||
| Eye disorders | Blepharitis Growth of eyelashes Lacrimation increased Ocular hyperaemia Dry eye Eye pruritus Eye irritation |
||||
| Cardiac disorders | Tachycardia | ||||
| Vascular disorders | Deep vein thrombosis Hypotension Hypertension Flushing |
||||
| Respiratory, thoracic and mediastinal disorders | Pulmonary embolism Epistaxis |
||||
| Gastrointestinal disorders | Rectal haemorrhage Dry mouth Dyspepsia Aphthous stomatitis Cheilitis Gastroesophageal reflux disease |
||||
| Skin and subcutaneous tissue disorders | Palmar-plantar erythrodysaesthesia syndrome Skin ulcer Scab Hypertrichosis Onychoclasis Nail disorder |
||||
| Musculoskeletal and connective tissue disorders | Pain in extremity | ||||
| General disorders and administration site conditions | Chest pain Pain Chills |
||||
| Investigations | Blood magnesium decreased | ||||
| MedDRA system organ class | Adverse reactions | ||||
|---|---|---|---|---|---|
| Uncommon (≥1/1000 to <1/100) | |||||
| Infections and infestations | Eye infection Eyelid infection |
||||
| Blood and lymphatic system disorders | |||||
| Immune system disorders | |||||
| Metabolism and nutrition disorders | |||||
| Psychiatric disorders | |||||
| Nervous system disorders | |||||
| Eye disorders | Eyelid irritation Keratitis |
||||
| Cardiac disorders | Cyanosis | ||||
| Vascular disorders | |||||
| Respiratory, thoracic and mediastinal disorders | Bronchospasm Nasal dryness |
||||
| Gastrointestinal disorders | Dry Lips | ||||
| Skin and subcutaneous tissue disorders | Angioedema Hirsutism Ingrowing nail Onycholysis |
||||
| Musculoskeletal and connective tissue disorders | |||||
| General disorders and administration site conditions | Infusion-related reaction | ||||
| Investigations | |||||
| MedDRA system organ class | Adverse reactions | ||||
|---|---|---|---|---|---|
| Rare (≥1/10,000 to <1/1000) | |||||
| Infections and infestations | |||||
| Blood and lymphatic system disorders | |||||
| Immune system disorders | Anaphylactic reaction | ||||
| Metabolism and nutrition disorders | |||||
| Psychiatric disorders | |||||
| Nervous system disorders | |||||
| Eye disorders | Ulcerative keratitis | ||||
| Cardiac disorders | |||||
| Vascular disorders | |||||
| Respiratory, thoracic and mediastinal disorders | |||||
| Gastrointestinal disorders | |||||
| Skin and subcutaneous tissue disorders | Skin necrosis | ||||
| Musculoskeletal and connective tissue disorders | |||||
| General disorders and administration site conditions | |||||
| Investigations | |||||
| MedDRA system organ class | Adverse reactions | ||||
|---|---|---|---|---|---|
| Frequency not known* | |||||
| Infections and infestations | |||||
| Blood and lymphatic system disorders | |||||
| Immune system disorders | |||||
| Metabolism and nutrition disorders | |||||
| Psychiatric disorders | |||||
| Nervous system disorders | |||||
| Eye disorders | |||||
| Cardiac disorders | |||||
| Vascular disorders | |||||
| Respiratory, thoracic and mediastinal disorders | Interstitial lung disease | ||||
| Gastrointestinal disorders | |||||
| Skin and subcutaneous tissue disorders | |||||
| Musculoskeletal and connective tissue disorders | |||||
| General disorders and administration site conditions | |||||
| Investigations | |||||
| MedDRA system organ class | Adverse reactions | ||||
|---|---|---|---|---|---|
| Very common (≥1/10) | Common (≥1/100 to <1/10) | Uncommon (≥1/1000 to <1/100) | Rare (≥1/10,000 to <1/1000) | Frequency not known* | |
| Infections and infestations | Paronychia | Rash pustular Cellulitis Folliculitis Localised infection |
Eye infection Eyelid infection |
||
| Blood and lymphatic system disorders | Anaemia | Leukopenia | |||
| Immune system disorders | Hypersensitivity | Anaphylactic reaction | |||
| Metabolism and nutrition disorders | Hypokalaemia Anorexia Hypomagnesaemia |
Hypocalcaemia Dehydration Hyperglycaemia Hypophosphataemia |
|||
| Psychiatric disorders | Insomnia | Anxiety | |||
| Nervous system disorders | Headache Dizziness |
||||
| Eye disorders | Conjunctivitis | Blepharitis Growth of eyelashes Lacrimation increased Ocular hyperaemia Dry eye Eye pruritus Eye irritation |
Eyelid irritation Keratitis |
Ulcerative keratitis | |
| Cardiac disorders | Tachycardia | Cyanosis | |||
| Vascular disorders | Deep vein thrombosis Hypotension Hypertension Flushing |
||||
| Respiratory, thoracic and mediastinal disorders | Dyspnoea Cough |
Pulmonary embolism Epistaxis |
Bronchospasm Nasal dryness |
Interstitial lung disease | |
| Gastrointestinal disorders | Diarrhoea Nausea Vomiting Abdominal pain Stomatitis Constipation |
Rectal haemorrhage Dry mouth Dyspepsia Aphthous stomatitis Cheilitis Gastroesophageal reflux disease |
Dry lips | ||
| Skin and subcutaneous tissue disorders | Dermatitis acneiform Rash† Erythema Pruritus Dry skin Skin fissures Acne Alopecia |
Palmar-plantar erythrodysaesthesia syndrome Skin ulcer Scab Hypertrichosis Onychoclasis Nail disorder Hyperhidrosis Dermatitis |
Angioedema Hirsutism Ingrowing nail Onycholysis |
Skin necrosis | |
| Musculoskeletal and connective tissue disorders | Back pain | Pain in extremity | |||
| General disorders and administration site conditions | Fatigue Pyrexia Asthenia Mucosal inflammation Oedema peripheral |
Chest pain Pain Chills |
Infusion-related reaction | ||
| Investigations | Weight decreased | Blood magnesium decreased | |||
*Frequency cannot be estimated from the available data. †Rash includes common terms of skin toxicity, skin exfoliation, exfoliative rash, rash papular, rash pruritic, rash erythematous, rash generalised, rash macular, rash maculopapular, skin lesion. MedDRA = Medical Dictionary for Regulatory Activities.
Infusion-related reactions
- Infusion-related reactions (occurring within 24 hours of an infusion) were reported in ~4% of patients treated with Vectibix®, of which <1% were severe (grade 3 and grade 4); fatal outcomes have been noted in rare post-marketing reports1
- Symptoms may include:1
- Headache
- Rashes
- Itching or hives
- Flushing
- Swelling (face, lips, mouth, around the eyes, and throat area)
- Rapid and irregular heartbeat
- Fast pulse
- Sweating
- Nausea
- Vomiting
- Dizziness
- Difficulty breathing or swallowing
- Decrease in blood pressure that may be severe or life-threatening and, very rarely, may lead to death
- Hypersensitivity reactions occurring more than 24 hours after infusion have been reported1
- If your patient experiences an infusion-related reaction, the Summary of Product Characteristics recommends to reduce the rate of infusion or discontinue Vectibix® treatment permanently if the reaction is severe or life-threatening1
- Vectibix® Summary of Product Characteristics.
- Cetuximab Summary of Product Characteristics.
- Lacouture E et al. J Clin Oncol 2010;28:1351–1357.
References:
Vectibix® dose adjustments
Skin toxicity1
Infusion-related reactions1
Mild or moderate (grade 1 or 2)
infusion-related reaction
Reduce infusion rate for the duration of that infusion
Maintain this lower infusion rate in all subsequent infusions
Severe or life-threatening* (grade 3 or 4) infusion-related reaction occurring during or any time after infusion
Permanently discontinue treatment
*For example: bronchospasm, angioedema, hypotension, need for parenteral treatment, or anaphylaxis1
Please see the Summary of Product Characteristics for more information
References:
- Vectibix® Summary of Product Characteristics.