Vectibix

/ Amgen

Vectibix treatment should be supervised by a physician experienced in the use of anti-cancer therapy.
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.
Posology: The recommended dose of Vectibix is 6 mg/kg of body weight given once every two weeks. Prior to infusion, Vectibix should be diluted in sodium chloride 9 mg/mL (0.9%) solution for injection to a final concentration not to exceed 10 mg/mL.
Modification of the dose of Vectibix may be necessary in cases of severe (≥ grade 3) dermatological reactions.
Special populations: The safety and efficacy of Vectibix have not been studied in patients with renal or hepatic impairment. There is no clinical data to support dose adjustments in the elderly.
Pediatric population: There is no relevant use of Vectibix in the pediatric population in the indication treatment of colorectal cancer.
Method of administration: Vectibix must be administered as an intravenous infusion via an infusion pump, using a low protein binding 0.2 or 0.22 micrometer in-line filter, through a peripheral line or indwelling catheter. The
recommended infusion time is approximately 60 minutes. If the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes. Doses higher than 1,000 mg should be infused over approximately 90 minutes.
The infusion line should be flushed with sodium chloride solution before and after Vectibix administration to avoid mixing with other medicinal products or intravenous solutions.
A reduction in the rate of infusion of Vectibix may be necessary in cases of infusion-related reactions.
Vectibix must not be administered as an intravenous push or bolus.

In combination with chemotherapy for the treatment of unresectable, advanced or recurrent colorectal cancer (mCRC) with wild-type RAS.
Monotherapy for the treatment of patients with metastatic colorectal carcinoma with wild-type RAS after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

Patients with a history of severe or life-threatening hypersensitivity reactions to the active substance or to any of the excipients.
Patients with interstitial pneumonitis or pulmonary fibrosis.
The combination of Vectibix with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant RAS mCRC or for whom RAS mCRC status is unknown.

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Dermatologic reactions and soft tissue toxicity: Dermatologic related reactions, a pharmacologic effect observed with epidermal growth factor receptor (EGFR) inhibitors, are experienced with nearly all patients (approximately 94%) treated with Vectibix. Severe (NCI-CTC grade 3) skin reactions were reported in 32% and life-threatening (NCI-CTC grade 4) skin reactions in < 1% of patients who received Vectibix in combination with chemotherapy (n = 1,172). For recommended dose modification see prescribing information.
Pulmonary complications: Patients with a history of, or evidence of, interstitial pneumonitis or pulmonary fibrosis were excluded from clinical studies. Cases of Interstitial Lung Disease (ILD), both fatal and non-fatal, have been reported, mainly from the Japanese population.
If ILD is diagnosed, Vectibix should be permanently discontinued and the patient should be treated appropriately. In patients with a history of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with panitumumab versus the risk of pulmonary complications must be carefully considered.
Electrolyte disturbances: Progressively decreasing serum magnesium levels leading to severe (grade 4) hypomagnesemia have been observed in some patients. Patients should be periodically monitored for hypomagnesemia and
accompanying hypocalcemia prior to initiating Vectibix treatment, and periodically thereafter for up to 8 weeks after the completion of treatment. Magnesium repletion is recommended, as appropriate.
Infusion-related reactions: Across monotherapy and combination mCRC clinical studies (n = 2,224), infusion-related reactions (occurring within 24 hours of an infusion) were reported in treated patients, including severe infusion-related reactions (NCI-CTC grade 3 and grade 4).
In the post-marketing setting, serious infusion-related reactions have been reported, including rare post-marketing reports with a fatal outcome. If a severe or life-threatening reaction occurs during an infusion or at any time post-infusion [e.g. presence of bronchospasm, angioedema, hypotension, need for parenteral treatment, or anaphylaxis], treatment should be permanently discontinued.
In patients experiencing a mild or moderate (CTCAE v 4.0 grades 1 and 2) infusion-related reaction the infusion rate should be reduced for the duration of that infusion. It is recommended to maintain this lower infusion rate in all subsequent infusions.
Hypersensitivity reactions occurring more than 24 hours after infusion have been reported including a fatal case of angioedema that occurred more than 24 hours after the infusion. Patients should be informed of the possibility of a late onset reaction and instructed to contact their physician if symptoms of a hypersensitivity reaction occur.
Acute renal failure: Acute renal failure has been observed in patients who develop severe diarrhea and dehydration. Patients who experience severe diarrhea should be instructed to consult a healthcare professional urgently.
See prescribing information for full details.

Based on an analysis of all mCRC clinical trial patients receiving Vectibix monotherapy and in combination with chemotherapy (n = 2,224), the most commonly reported adverse reactions are skin reactions occurring in approximately 94% of patients. These reactions are related to the pharmacologic effects of Vectibix, and the majority are mild to moderate in nature with 23% severe (grade 3 NCI-CTC) and < 1% life-threatening (grade 4 NCI-CTC).
Very commonly reported adverse reactions occurring in ≥ 20% of patients were gastrointestinal disorders [diarrhea (46%), nausea (39%), vomiting (26%), constipation (23%) and abdominal pain (23%)]; general disorders [fatigue (35%), pyrexia (21%)]; metabolism and nutrition disorders [decreased appetite (30%)]; infections and infestations [paronychia (20%)]; and skin and subcutaneous disorders [rash (47%), dermatitis acneiform (39%), pruritus (36%), erythema (33%) and dry skin (21%)].
See prescribing information for full details.

Data from an interaction study involving Vectibix and irinotecan in patients with mCRC indicated that the pharmacokinetics of irinotecan and its active metabolite, SN-38, are not altered when the medicinal products are co-administered. Results from a cross-study comparison indicated that irinotecan-containing regimens (IFL or FOLFIRI) have no effect on the pharmacokinetics of
panitumumab.
Vectibix should not be administered in combination with IFL chemotherapy or with bevacizumab-containing chemotherapy. A high incidence of severe diarrhea was observed when panitumumab was administered in combination with IFL, and increased toxicity and deaths were seen when panitumumab was combined with bevacizumab and chemotherapy.
The combination of Vectibix with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant RAS mCRC or for whom RAS mCRC status is unknown. A shortened progression-free survival and overall survival time were observed in a clinical study in patients with mutant RAS tumors who received panitumumab and FOLFOX.

Pregnancy: In women of childbearing potential, appropriate contraceptive measures must be used during treatment with Vectibix, and for 2 months following the last dose. If Vectibix is used during pregnancy or if the patient becomes pregnant while receiving this medicinal product, she should be advised of the potential risk for loss of the pregnancy or potential hazard to the fetus.
Lactation: It is unknown whether panitumumab is excreted in human breast milk. Because human IgG is secreted into human milk, panitumumab might also be secreted. The potential for absorption and harm to the infant after ingestion is unknown. It is recommended that women do not breast-feed during treatment with Vectibix and for 2 months after the last dose.
See prescribing information for full details.

Doses up to 9 mg/kg have been tested in clinical trials. There have been reports of overdose at doses up to approximately twice the recommended therapeutic dose (12 mg/kg). Adverse events observed included skin toxicity, diarrhea, dehydration and fatigue and were consistent with the safety profile at the recommended dose.

Storage: Store in a refrigerator (2°C – 8°C). Do not freeze. Store in the original carton in order to protect from light.