Usage
Avelumab (Bavencio) is prescribed for the treatment of several types of cancer:
- Metastatic Merkel Cell Carcinoma (MCC): In adults and pediatric patients 12 years and older.
- Urothelial Carcinoma (UC): As maintenance therapy for locally advanced or metastatic UC that hasn’t progressed after first-line platinum-containing chemotherapy. It’s also used for locally advanced or metastatic UC that progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
- Renal Cell Carcinoma (RCC): As first-line treatment, in combination with axitinib, for patients with advanced RCC.
Pharmacological Classification: Avelumab is a programmed death ligand-1 (PD-L1) blocking antibody, classified as an immune checkpoint inhibitor.
Mechanism of Action: Avelumab binds to PD-L1, preventing its interaction with the PD-1 receptor on T cells. This blockade inhibits the downregulation of the immune response, allowing T cells to recognize and attack cancer cells.
Alternate Names
Avelumab is also known by its brand name, Bavencio. There are no widely used alternate names or regional variations.
How It Works
Pharmacodynamics: Avelumab enhances the anti-tumor immune response by blocking the PD-1/PD-L1 pathway. This leads to increased T-cell activation and proliferation, promoting tumor cell death.
Pharmacokinetics:
- Absorption: Administered intravenously, so bioavailability is 100%.
- Distribution: The mean volume of distribution at steady state is approximately 4.7 L.
- Metabolism: Primarily metabolized via catabolic pathways. Drug-drug interactions due to metabolic pathways are not expected.
- Elimination: The primary elimination mechanism is catabolism.
Mode of Action: Avelumab specifically targets the PD-L1 protein expressed on tumor cells and some immune cells. By binding to PD-L1, avelumab prevents the interaction between PD-L1 and PD-1, thereby releasing the “brakes” on the immune system.
Receptor Binding/Enzyme Inhibition: Avelumab’s primary mechanism involves receptor binding to PD-L1. It doesn’t directly inhibit enzymes or modulate neurotransmitters.
Elimination Pathways: Avelumab is eliminated primarily through catabolic pathways, similar to the breakdown of endogenous proteins.
Dosage
Standard Dosage
Adults:
- MCC, UC: 800 mg every 2 weeks as an intravenous infusion over 60 minutes.
- RCC (in combination with axitinib): Avelumab 800 mg every 2 weeks as an intravenous infusion over 60 minutes, along with axitinib 5 mg orally twice daily.
Children:
- MCC: For patients 12 years and older, the dosage is the same as for adults (800 mg every 2 weeks).
- Safety and efficacy haven’t been established in children under 12.
Special Cases:
- Elderly Patients: No dose adjustment is typically necessary.
- Patients with Renal Impairment: No dose adjustment for mild or moderate impairment. Insufficient data for severe renal impairment.
- Patients with Hepatic Dysfunction: No dose adjustment for mild impairment. Insufficient data for moderate or severe impairment.
- Patients with Comorbid Conditions: Close monitoring is necessary for patients with cardiovascular risk factors (e.g., hypertension, diabetes mellitus, dyslipidemia).
Clinical Use Cases
The specific dosages mentioned above apply to the clinical use cases of MCC, UC, and RCC. Avelumab is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
Dose adjustments are not routinely recommended but might be necessary based on individual tolerability and the development of adverse events, particularly immune-related adverse events.
Side Effects
Common Side Effects:
Fatigue, musculoskeletal pain, infusion-related reactions, rash, nausea, constipation, cough, diarrhea.
Rare but Serious Side Effects:
Immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies (thyroid disorders, adrenal insufficiency, type 1 diabetes mellitus), nephritis, myocarditis.
Long-Term Effects:
The long-term effects of avelumab are still being studied, but potential long-term complications can include chronic fatigue, persistent endocrinopathies, and secondary malignancies.
Adverse Drug Reactions (ADR):
Severe infusion-related reactions, immune-mediated adverse events.
Contraindications
Hypersensitivity to avelumab.
Drug Interactions
No formal drug interaction studies have been conducted. Avelumab is primarily metabolized by catabolic pathways, so drug-drug interactions are not anticipated. However, concomitant use of systemic corticosteroids or immunosuppressants should be avoided before starting avelumab because they might interfere with its efficacy. These medications can be used after starting avelumab to manage immune-related adverse reactions.
Pregnancy and Breastfeeding
Pregnancy Safety Category: Avelumab can cause fetal harm, including fetal death. Women of childbearing potential should use effective contraception during treatment and for at least one month after the last dose.
Breastfeeding: Avelumab may be excreted in breast milk. Breastfeeding should be avoided during treatment and for at least one month after the final dose.
Drug Profile Summary
- Mechanism of Action: PD-L1 blocking antibody, enhancing anti-tumor immune response.
- Side Effects: Fatigue, musculoskeletal pain, infusion reactions, rash, nausea, diarrhea; serious immune-related adverse events possible.
- Contraindications: Hypersensitivity to avelumab.
- Drug Interactions: No formal studies; interactions not expected due to catabolic metabolism.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; breastfeeding should be avoided.
- Dosage: 800 mg IV every 2 weeks; pediatric dosing same as adults for patients ≥12 years old.
- Monitoring Parameters: Monitor for immune-related adverse events, vital signs, blood counts, liver and thyroid function tests.
Popular Combinations
- Avelumab + Axitinib (for advanced RCC).
Precautions
- Monitor for immune-related adverse events.
- Premedication with antihistamines and paracetamol prior to the first four infusions and as needed.
- Evaluate patients for pre-existing medical conditions, especially autoimmune diseases.
- Avoid concomitant use of systemic corticosteroids or immunosuppressants prior to starting avelumab.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Avelumab?
A: 800 mg intravenously every 2 weeks for adults and pediatric patients 12 years and older.
Q2: How is Avelumab administered?
A: Administered as an intravenous infusion over 60 minutes.
Q3: What are the most common side effects of Avelumab?
A: Fatigue, musculoskeletal pain, infusion-related reactions, rash, nausea, constipation, cough, and diarrhea.
Q4: What are the serious side effects to watch out for with Avelumab?
A: Immune-mediated adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Q5: Can Avelumab be used during pregnancy or breastfeeding?
A: No, Avelumab is contraindicated during pregnancy and breastfeeding.
Q6: Are there any specific drug interactions with Avelumab?
A: No formal interaction studies have been conducted, and interactions are not expected due to catabolic metabolism; however, caution should be exercised with concomitant immunosuppressants or corticosteroids.
Q7: What premedication is recommended before Avelumab infusion?
A: Premedication with an antihistamine and paracetamol is recommended for the first four infusions and as clinically indicated for subsequent infusions.
A: Management of immune-related adverse events varies depending on the specific event and severity, including withholding avelumab, administering corticosteroids, and providing supportive care.
Q9: Does Avelumab require dose adjustments for elderly patients?
A: Generally, no dose adjustments are needed for elderly patients.
Q10: What is the mechanism of action of Avelumab?
A: Avelumab is a PD-L1 blocking antibody that enhances the anti-tumor immune response by preventing PD-L1 from interacting with the PD-1 receptor on T cells.
