DefinitionThis section has been translated automatically.
Intravenously administrable, biotechnologically produced, human monoclonal IgG1λ antibody approved for the treatment of patients with metastatic Merkel cell carcinoma and other cancers. Avelumab was approved in the US, EU and Switzerland in 2017.
Pharmacodynamics (Effect)This section has been translated automatically.
Avelumab binds to the programmed cell death ligand 1(PD-L1) and thus prevents interaction with the receptors PD-1 and B7.1. The protein has immunostimulatory, antitumour and cytotoxic properties and thereby inhibits the interaction between PD-L1 and the receptors PD-1 and B7.1, which leads to the inhibitory effect of PD-L1 on the T-cells being cancelled. Cytotoxic T cells, T cell proliferation and cytokine production are stimulated.
PD-L1 is expressed on tumour cells and/or tumour-infiltrating immune cells and inhibits the immune response. In vitro, however, Avelumab has been shown to additionally mediate direct tumor cell lysis by means of antibody dependent cell-mediated cytotoxicity (ADCC). The half-life of the therapeutic agent is about 6 days
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IndicationThis section has been translated automatically.
Metastatic Merkel cell carcinoma (D'Angelo SP et al. 2018).
In some countries extended indications: urothelial carcinoma, stomach cancer.
Avelumab is used in combination with axitinib as first-line therapy in adult patients with advanced renal cell carcinoma (RCC) (Choueiri TK et al. 2018).
Dosage and method of useThis section has been translated automatically.
The recommended dose of Bavencio as monotherapy is 800 mg every 2 weeks and is administered intravenously for 60 minutes.
Premedication: Before the first 4 infusions of Bavencio, patients must be premedicated with an antihistamine and paracetamol. If the fourth infusion is completed without an infusion-related reaction, premedication should be administered at subsequent doses at the discretion of the physician.
Undesirable effectsThis section has been translated automatically.
Note: Side effects are classified by system organ class and frequency. The frequencies are defined as follows: very frequent (≥ 1/10); frequent (≥ 1/100, < 1/10); occasional (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000). Within each frequency group, the side effects are listed according to decreasing severity. The organ and disease classes (SOC) are named after MedDRA.
The most common possible adverse effects include:
fatigue, nausea, diarrhoea, loss of appetite, constipation, infusion-related reactions, weight loss and vomiting.
ADRs in a stdie (Merkel cell carcinoma: safety and side effects of monotherapy with Avelumab in 1,738 patients with solid tumours, including metastatic MCC). These patients received Avelumab 10 mg/kg every 2 weeks in clinical trials. In this patient population, the most common side effects associated with Avelumab were fatigue (32.4%), nausea (25.1%), diarrhea (18.9%), reduced appetite (18.4%), constipation (18.4%), infusion-related reactions (17.1%), weight loss (16.6%) and vomiting (16.2%). The most common adverse events ≥ 3rd degree were anaemia (6.0%), dyspnoea (3.9%) and abdominal pain (3.0%). Serious adverse events were immune-mediated side effects and infusion-related reactions
Diseases of the blood and lymphatic system
- Very often: Anemia
- Common: Lymphopenia
- Occasionally: thrombocytopenia, eosinophilia
Diseases of the immune system
- Occasionally: drug hypersensitivity, anaphylactic hypersensitivity reaction, type 1 hypersensitivity
- Common: Hypothyroidism
- Occasionally: Adrenal insufficiency, hyperthyroidism, thyroiditis, autoimmune thyroiditis, acute adrenal insufficiency, autoimmune hypothyroidism, hypopituitarism
Metabolic and nutritional disorders
- Very often: Reduced appetite
- Occasionally: Diabetes mellitus*, diabetes mellitus type 1
diseases of the nervous system
- Common: headache, dizziness, peripheral neuropathy
- Occasionally: Guillain-Barré syndrome*
- Occasionally: Uveitis
- Rare: Myocarditis
- Common: Hypertension, hypotension
- Occasionally: Flush
Diseases of the respiratory tract, chest and mediastinum
- Very often: cough, dyspnea
- Common: Pneumonitis
diseases of the gastrointestinal tract
- Very often: nausea, diarrhoea, constipation, vomiting, abdominal pain
- Frequently: Dry mouth
- Occasionally: colitis, autoimmune colitis, enterocolitis, ileus
- Rare: Pancreatitis
Liver and bile diseases
- Occasionally: Autoimmune hepatitis, acute liver failure, hepatitis
Diseases of the skin and subcutaneous tissue:
- Common: Pruritus, maculo-papular exanthema, dry skin
- Occasionally: psoriasis, exfoliative dermatitis, erythema multiforme, pemphigoid, generalized pruritus, vitiligo (Wang PF et al 2017)
Skeletal muscle, connective tissue and bone diseases
- Very often: back pain, arthralgia
- Common: Myalgia
- Occasionally: Myositis
In < 1% of patients, other clinically significant immune-mediated adverse events were reported: myositis, hypopituitarism, uveitis and Guillain-Barré syndrome (Wang PF et al. 2017).
ContraindicationThis section has been translated automatically.
Avelumab is contraindicated in hypersensitivity. Full precautions are given in the drug information leaflet.
PreparationsThis section has been translated automatically.
Note(s)This section has been translated automatically.
Patients should be monitored for signs and symptoms of infusion-related reactions such as fever, chills, sensation of heat, hypotension, dyspnoea, wheezing, back pain, abdominal pain and urticaria.
LiteratureThis section has been translated automatically.
- Pharmaceutical information leaflet (Merck); accessed on 27.8.2020
- Choueiri TK et al (2018) Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol 19: 451-460.
- D'Angelo SP et al (2018) Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma: A Preplanned Interim Analysis of a Clinical Trial. JAMA Oncol 4:e180077.
- Dirix LY et al (2018) Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treatment 167: 671-686.
- Gaiser MR et al (2018) PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma. Expert Rev Clin Pharmacol 11:345-359.
- Joseph J et al (2018) Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma. Ann Pharmacother 52:928-935.
- Wang PF et al (2017) Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis. Front Pharmacol 8:730.