Avelumab

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.

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

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).

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.

Note: Adverse reactions are ordered by system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10); common (≥ 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, adverse reactions are listed by decreasing severity. Organ and disease classes (SOC) are named according to MedDRA.

The most common potential adverse effects include:

Fatigue, nausea, diarrhea, loss of appetite, constipation, infusion-related reactions, weight loss, and vomiting.

Adverse events in the setting of a stdie (Merkel cell carcinoma: safety and adverse events of monotherapy with avelumab in 1,738 patients with solid tumors, including metastatic MCC). These patients received avelumab 10 mg/kg every 2 weeks in clinical trials. In this patient population, the most common adverse reactions experienced with avelumab were fatigue (32.4%), nausea (25.1%), diarrhea (18.9%), decreased appetite (18.4%), constipation (18.4%), infusion-related reactions (17.1%), weight loss (16.6%), and vomiting (16.2%). The most common adverse reactions ≥ 3rd degree were anemia (6.0%), dyspnea (3.9%), and abdominal pain (3.0%). Serious adverse reactions were immune-mediated adverse reactions and infusion-related reactions

Blood and lymphatic system disorders

• Very common: anemia
• Frequent: lymphopenia
• Occasional: thrombocytopenia, eosinophilia

Immune system disorders

• Occasionally: drug hypersensitivity, anaphylactic hypersensitivity reaction, type 1 hypersensitivity

Endocrine disorders

• Frequent: hypothyroidism
• Occasional: adrenal insufficiency, hyperthyroidism, thyroiditis, autoimmune thyroiditis, acute adrenal insufficiency, autoimmune hypothyroidism, hypopituitarism

Metabolic and nutritional disorders

• Very common: decreased appetite
• Occasionally: diabetes mellitus*, diabetes mellitus type 1

Nervous system disorders

• Frequent: headache, dizziness, peripheral neuropathy
• Occasionally: Guillain-Barré syndrome*

Eye diseases

• Occasional: Uveitis

Heart disease

• Rarely: Myocarditis

Vascular disorders

• Frequent: Hypertension, hypotension
• Occasionally: Flush

Respiratory, thoracic and mediastinal disorders

• Very common: Cough, dyspnea
• Frequently: Pneumonitis

Gastrointestinal disorders

• Very common: nausea, diarrhea, constipation, vomiting, abdominal pain
• Frequently: dry mouth
• Occasional: colitis, autoimmune colitis, enterocolitis, ileus
• Rarely: pancreatitis

Liver and biliary disorders

• Occasional: autoimmune hepatitis, acute liver failure, hepatitis

Skin and subcutaneous tissue disorders:

• Frequent: pruritus, maculo-papular exanthema, dry skin.
• Occasional: psoriasis, exfoliative dermatitis, erythema multiforme, pemphigoid, generalized pruritus, vitiligo (Wang PF et al 2017).

Skeletal muscle, connective tissue, and bone disorders.

• Very common: back pain, arthralgia.
• Frequent: Myalgia
• Occasional: myositis

In < 1% of patients, other clinically significant immune-mediated adverse events have been reported: myositis, hypopituitarism, uveitis, and Guillain-Barré syndrome (Wang PF et al 2017).

Avelumab is contraindicated in hypersensitivity. Full precautions are given in the drug information leaflet.

Bavencio®

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.

1. Pharmaceutical information leaflet (Merck); accessed on 27.8.2020
2. 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.
3. 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.
4. 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.
5. Gaiser MR et al (2018) PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma. Expert Rev Clin Pharmacol 11:345-359.
6. Joseph J et al (2018) Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma. Ann Pharmacother 52:928-935.
7. 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.