维必施Vectibix（帕尼单抗注射液）

【Function and Indications】
(1) Vectibix is ​​an epidermal growth factor receptor antagonist indicated for monotherapy or treatment of metastatic colorectal cancer with disease progression following fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy. Approval is based on progression-free survival; there is no data demonstrating that Vectibix improves disease-related symptoms or increases survival.
(2) Retrospective subgroup analysis of metastatic colon cancer trials has not shown a therapeutic benefit for patients with tumors that have KRAS mutations in codons 12 or 13; Vectibix is ​​not recommended for the treatment of colorectal cancer with these mutations.

[Model and Specifications]
Single-use vial (20 mg/mL): 100 mg/5 mL, 200 mg/10 mL, 400 mg/20 mL

[Usage and Dosage]
(1) Administer 6 mg/kg every 14 days, intravenously over 60 minutes (≤ 1000 mg) or 90 minutes (> 1000 mg).

(2) Infusion reactions: Slow down the infusion rate by 50% for mild reactions; terminate the infusion for severe infusion reactions. Depending on the severity and/or persistence of the reaction, permanently discontinue Vectibix.

(3) Dermatological toxicity: Do not administer for severe or intolerable toxicity; resume at half the dose if toxicity improves.

[Clinical Studies]
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice. However, adverse reaction data from clinical studies do provide a basis for identifying adverse events associated with drug use and approximate rates. Safety data from 15 clinical trials in which 1467 patients received Vectibix; 1293 of these received Vectibix monotherapy and 174 received Vectibix in combination with chemotherapy.
An open-label, multinational, randomized, controlled trial investigated the safety and efficacy of Vectibix in 463 patients with EGFR-expressing, metastatic colorectal cancer (mCRC). Patients were required to have progressed after treatment with a regimen containing one or more fluoropyrimidines, oxaliplatin, and irinotecan; progression was confirmed by an independent review committee (IRC) in 75% of patients. All patients were required to have EGFR expression defined as at least 1+ membrane staining in ≥ 1% of tumor-resistant cells using the Dako EGFR pharmDx? Assay Kit. Patients were randomized 1:1 to receive panitumumab at a dose of 6 mg/kg given every 2 weeks plus best supportive care (BSC) (n = 231) or BSC alone (n = 232) until investigator-determined disease progression. Randomization was stratified by ECOG performance status (0–1 vs. 2) and geographic region (Western Europe, Eastern/Central Europe, or Other). Patients were eligible to receive panitumumab in the BSC-alone group based on investigator-determined disease progression and were followed until IRC-confirmed disease progression. Analyses of progression-free survival (PFS), objective response, and duration of response were based on events confirmed by the IRC blinded to assigned treatment. Of the 463 patients, 63% were male, the median age was 62 years, 40% were 65 years or older, 99% were white, 86% had a baseline ECOG performance status of 0 or 1, and 67% had colon cancer. The median number of previous therapies for metastatic disease was 2.4. Tumors had membrane-staining intensity for EGFR of 3+ in 19% of patients, 2+ in 51%, and 1+ in 30%. The percentage of tumor cells with EGFR membrane staining in the following categories > 35%, > 20%–35%, 10%–20%, and 1%–< 10% were 38%, 8%, 31%, and 22%, respectively. Based on disease progression as determined by IRC, statistically significant prolongation of PFS was observed in patients receiving Vectibix compared with patients receiving BSC alone. The mean PFS was 96 days in the Vectibix group and 60 days in the BSC-alone group.

【Precautions】
(1) Dermatological toxicity: Withhold or discontinue Vectibix and monitor patients for inflammatory or infectious sequelae of severe dermatological toxicity. Limit sun exposure.
(2) Infusion reactions: Stop infusion for severe infusion reactions.
(3) Increased toxicity with chemotherapy: Vectibix is ​​not indicated for use in combination with chemotherapy.
(4) Pulmonary fibrosis: Discontinue Vectibix in patients who develop interstitial lung disease, pneumonitis, or pulmonary infiltrates.
(5) Electrolyte depletion/monitoring: Monitor electrolytes and initiate appropriate treatment for 8 weeks during and after treatment with Vectibix.

(6) Ocular toxicity: Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix for acute or worsening keratitis.

[Adverse Reactions and Contraindications]
The most common adverse reactions (≥ 20%) are skin toxicity (i.e., erythema, acneiform dermatitis, pruritus, exfoliation, rash, and cracks), paronychia, hypomagnesemia, fatigue, abdominal pain, diarrhea, and constipation.

[Use in Pregnant Women]
Based on animal data, fetal harm may occur.

[Use in Children]
The safety and efficacy of Vectibix in children have not been established.

[Drug Interactions]
Vectibix is ​​not suitable for use in combination with chemotherapy. No formal drug-drug interaction studies have been conducted with Vectibix.

【Storage】
Store the vial in the original box in a refrigerator at 2° to 8°C (36° to 46°F) until use. Protect from direct sunlight. Do not freeze. Because Vectibix does not contain a preservative, any unused portion remaining in the vial must be discarded. The diluted Vectibix infusion solution should be used within 6 hours of preparation if stored in a refrigerator at 2° to 8°C (36° to 46°F), or within 24 hours of dilution at room temperature. Do not freeze.

【Manufacturer】
GSK