阿维鲁单抗(Avelumab)中文说明书:适应症、用法用量、不良反应、注意事项

Avelumab is a PD-L1 inhibitor anti-tumor drug jointly developed by Pfizer and Merck of Germany. It was first approved by the FDA in March 2017. As a programmed death ligand-1 (PD-L1) blocking antibody, its mechanism of action is to relieve the immunosuppressive state in the tumor microenvironment by specifically binding to key proteins in the PD-1/PD-L1 immune checkpoint pathway (this pathway is expressed on the surface of immune cells and various tumor cells), thereby enhancing the ability of T cells to recognize and kill cancer cells.

Avelumab (Avelumab) indications

1. Metastatic Merkel cell carcinoma

Avelumab (avelumab) is suitable for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).

2. Locally advanced or metastatic urothelial carcinoma

(1) Avelumab is suitable for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) who have not progressed on first-line platinum-containing chemotherapy.

(2) Avelumab is suitable for the treatment of patients with previously treated locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or after platinum-containing chemotherapy, or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

3. Advanced renal cell carcinoma

Avelumab combined with axitinib is suitable for first-line treatment of patients with advanced renal cell carcinoma (RCC).

Avelumab usage and dosage

1. Recommended dose for pediatric patients

Merkel cell carcinoma

Adolescents ≥12 years old: 10 mg/kg every 2 weeks. Continue treatment until disease progression or unacceptable toxicity.

2. Recommended dose for adult patients

(1) Merkel cell carcinoma

Avelumab 10 mg/kg every 2 weeks. Continue treatment until disease progression or unacceptable toxicity.

(2) Urothelial carcinoma

Avelumab 10 mg/kg every 2 weeks. Continue treatment until disease progression or unacceptable toxicity.

Due to limited space, please refer to the original instructions of the drug for details. Please follow the guidance of your doctor for specific medication.

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Adverse reactions of Avelumab

1. Metastatic Merkel cell carcinoma

Fatigue, musculoskeletal pain, diarrhea, infusion-related reactions, nausea , rash, loss of appetite, peripheral edema, cough, constipation, abdominal pain, arthralgia, weight loss, dizziness, hypertension, vomiting, dyspnea, headache, pruritus, lymphopenia, anemia, elevated ALT and AST concentrations, thrombocytopenia, elevated lipase concentration.

2. Locally advanced or metastatic urothelial carcinoma

Fatigue, infusion-related reactions, musculoskeletal pain, nausea, loss of appetite, urinary tract infection, abdominal pain, weight loss, constipation, diarrhea, dyspnea (including exertional dyspnea), peripheral edema, elevated S chromium concentration/kidney Failure, fever, rash, cough, vomiting/retching, hypertension (including hypertensive crisis), pruritus, hyponatremia, elevated gamma-glutamyl transferase (γ-glutamyl transpeptidase, GGT, GGTP) concentrations, lymphopenia, hyperglycemia, elevated alkaline phosphatase concentrations, anemia, elevated lipase concentrations.

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Avelumab (Avelumab) Precautions

1. Immune-mediated pneumonia

According to reports, immune-mediated pneumonia is sometimes fatal. Monitor patients for signs of pneumonia. If pneumonia is suspected, evaluate with radiologic imaging. If immune-mediated pneumonitis occurs, temporarily withhold or discontinue avelumab. (See Immune-Mediated Pneumonitis under Dosage and Administration. If grade 2 or worse pneumonitis occurs, initiate systemic corticosteroid therapy (1-2 mg/kg prednisone [or equivalent] daily) and then gradually reduce the corticosteroid dose.

2. Immune-Mediated Hepatic Effects

Immune-mediated hepatitis has been reported to be sometimes fatal. Monitor patients for signs of hepatitis. Assess liver function tests (i.e., ALT, AST, total bilirubin) before initiation of treatment and periodically during treatment. Temporarily discontinue or discontinue avelumab if immune-mediated hepatitis occurs. If grade 2 or more severe hepatitis occurs, initiate systemic corticosteroid therapy (1-2 mg/kg prednisone [or equivalent] daily) and gradually reduce the corticosteroid dose.

3. Immune-mediated gastrointestinal effects

Immune-mediated colitis was reported. Monitor patients for signs of colitis and temporarily withhold or discontinue avelumab if immune-mediated colitis occurs. If grade 2 or worse colitis occurs, initiate systemic corticosteroid therapy (1 to 2 mg/kg prednisone [or equivalent] daily) and gradually reduce the corticosteroid dose.

4. Immune-mediated endocrine effects

Immune-mediated endocrinological diseases, such as thyroid dysfunction (i.e., hypothyroidism, hyperthyroidism), adrenal insufficiency, and diabetes (including ketoacidosis), have been reported.

5. Adrenocortical insufficiency

Monitor the symptoms of adrenal insufficiency. Temporarily discontinue avelumab if grade 3 or 4 immune-mediated adrenocortical insufficiency occurs. Initiate systemic corticosteroid therapy as clinically indicated.

6. Thyroid dysfunction

Monitor the symptoms of thyroid dysfunction. Assess thyroid function before initiation of treatment and periodically during treatment and then as clinically indicated. Temporarily discontinue avelumab if grade 3 or 4 immune-mediated thyroid dysfunction occurs. If immune-mediated hypothyroidism occurs, thyroid hormone replacement therapy should be initiated. If immune-mediated hyperthyroidism occurs, initiate appropriate medical therapy as clinically indicated.

7. Diabetes

Monitor the symptoms of type 1 diabetes. If grade 3 or higher type 1 diabetes develops, temporarily discontinue avelumab and initiate antidiabetic therapy (i.e., insulin). Once blood glucose concentrations have stabilized on antidiabetic therapy, resume avelumab.

8. Immune-mediated renal effects

Immune-mediated nephritis has been reported. Monitor patients for signs of nephritis. Assess S chromium concentrations before starting and periodically during treatment. Temporarily discontinue or discontinue avelumab if immune-mediated nephritis occurs. If grade 2 or worse nephritis occurs, initiate systemic corticosteroid therapy (1 to 2 mg/kg prednisone [or equivalent] daily) and gradually reduce the corticosteroid dose.

9. Other immune-mediated effects

Other immune-mediated adverse reactions, sometimes serious or fatal, have been reported with avelumab. If immune-mediated adverse reactions are suspected, temporarily withhold or discontinue avelumab. Depending on the severity, initiate high-dose corticosteroid therapy and then taper the corticosteroid dose; if indicated, initiate hormone replacement therapy.

10. Infusion-related effects

Infusion-related reactions, sometimes serious or life-threatening, have been reported. The first 4 avelumab infusions were preceded by acetaminophen and antihistamines. Monitor patients for signs of infusion-related reactions. If an infusion-related reaction occurs, the infusion should be interrupted, the infusion rate reduced, or avelumab should be permanently discontinued.

11. Fetal/neonatal morbidity and mortality

May cause harm to the fetus. It may destroy the mother's immune tolerance to the fetus and increase the risk of fetal miscarriage (miscarriage, stillbirth); it may also increase the risk of immune-mediated diseases. Avoid becoming pregnant during treatment. Women of childbearing potential should use an effective method of contraception during treatment with avelumab and for ≥1 month after discontinuation of treatment. If used during pregnancy or if the patient becomes pregnant, be aware of the potential fetal hazard.

12. Immunogenicity

Immunogenic potential. reported the development of antibodies conjugated to avelumab. No effects on safety (including infusion-related reactions) or drug pharmacokinetics were observed.