Avelumab

Avelumab is used in adults with metastatic Merkel cell carcinoma (MCC); in disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; in combination with axitinib for first-line treatment in patients with advanced renal cell carcinoma (RCC).

Avelumab is available under the following different brand names: Bavencio.

Dosages of Avelumab:

Dosage Forms and Strengths

Injectable Solution

• 20mg/mL (200mg/10mL single-dose vial)

Dosage Considerations – Should be Given as Follows:

Merkel Cell Carcinoma

• Indicated in adults with metastatic Merkel cell carcinoma (MCC)
• Adults and children 12 years and older: 800 mg intravenously (IV) every 2 weeks
• Continue until disease progression or unacceptable toxicity
• Children under 12 years: Safety and efficacy not established

Locally Advanced or Metastatic Urothelial Carcinoma

• Indicated in disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
• 800 mg IV every 2 weeks
• Continue until disease progression or unacceptable toxicity

Renal Cell Carcinoma

• Indicated in combination with axitinib for first-line treatment in patients with advanced renal cell carcinoma (RCC)
• Avelumab 800 mg IV every 2 weeks in combination with
• Axitinib 5 mg PO BID
• Continue until disease progression or unacceptable toxicity
• When axitinib is used in combination with avelumab, consider dose escalation of axitinib above the initial 5-mg dose at 2-week or greater intervals
• Refer also to prescribing information for axitinib dosing information

Dosage Modifications

Interrupt or slow infusion rate: Grade 1 or 2 infusion-related reaction

Withhold treatment (resume when recovery to grade up to 1 after corticosteroid taper)

• Grade 2 pneumonitis
• Grade 2 or 3 diarrhea or colitis
• Grade 3 or 4 endocrinopathies (including but not limited to hypothyroidism, hyperthyroidism, adrenal insufficiency, or hyperglycemia)
• Serum creatinine greater than 1.5 and up to 6 times ULN
• AST or ALT greater than 3 times and up to 5 times ULN or total bilirubin greater than 1.5 and up to 3 times ULN
• Moderate or severe clinical signs or symptoms of an immune-mediated adverse reaction (including but not limited to myocarditis, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, bullous dermatitis, Stevens-Johnson syndrome [SJS]/toxic epidermal necrolysis [TEN], pancreatitis, rhabdomyolysis, myasthenia gravis, histiocytic necrotizing lymphadenitis, demyelination, vasculitis, hemolytic anemia, hypophysitis, iritis, and
• encephalitis)

Permanently discontinue

• Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy)
• Grade 3 or 4 pneumonitis or recurrent Grade 2 pneumonitis
• Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis
• Serum creatinine greater than 6 times ULN
• AST or ALT greater than 5 times ULN or total bilirubin greater than 3 times ULN
• Grade 3 or 4 infusion-related reactions
• Inability to reduce corticosteroid dose to 10 mg/day or greater of prednisone or equivalent within 12 weeks
• Persistent Grade 2 or 3 immune-mediated adverse reactions lasting 12 weeks or greater
• Recurrent severe immune-mediated adverse reaction

RCC treated with avelumab in combination with axitinib

• ALT/AST 3 times or greater to less than 5 times ULN or total bilirubin 1.5 times or greater to less than 3 times ULN
  • Withhold both avelumab and axitinib until these reactions recover to grade up to 1
  • If persistent (more than 5 days), consider corticosteroid therapy (initial dose of 0.5-1 mg/kg/day) prednisone or equivalent followed by a taper
  • Consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery
  • If rechallenging axitinib, reduce dose per axitinib full prescribing information
• ALT/AST 5 times ULN or greater than 3 times ULN with concurrent total bilirubin 2 times ULN or greater or
• Permanently discontinue both avelumab and axitinib
• Consider corticosteroid therapy

Common side effects of avelumab include:

• Fatigue
• Low white blood cell count (lymphopenia, neutropenia)
• Anemia
• Increased AST
• Infusion-related reaction
• Low platelets (thrombocytopenia)
• Musculoskeletal pain
• Diarrhea
• Nausea
• Rash
• Urinary tract infection (UTI)
• Decreased appetite
• Swelling of extremities
• Increased ALT
• Abdominal pain
• Weight loss
• Increased creatinine/renal failure
• Fever
• Increased lipase
• Cough
• Constipation
• Shortness of breath
• Low blood sodium (hyponatremia)
• Joint pain
• Dizziness
• Vomiting/retching
• High blood pressure (hypertension)
• Increased GGT
• Itching
• Headache
• Increased amylase
• High blood sugar (hyperglycemia)
• Increased bilirubin
• Thyroid disorders
• Colitis
• Pneumonitis

Less common side effects of avelumab include:

• Hepatitis
• Adrenal insufficiency
• Type 1 diabetes mellitus
• Nephritis

Postmarketing side effects of avelumab reported include:

• Pancreatitis
• Myocarditis
• Myositis
• Congestive heart failure
• Heart attack (myocardial infarction)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Avelumab has no listed severe interactions with other drugs.
• Avelumab has no listed serious interactions with other drugs.
• Avelumab has no listed moderate interactions with other drugs.
• Avelumab has no listed mild interactions with other drugs.

Warnings

This medication contains avelumab. Do not take Bavencio if you are allergic to avelumab or any ingredients contained in this drug.

Contraindications

• None

Effects of Drug Abuse

• No information is available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Avelumab?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Avelumab?"

Cautions

Embryofetal toxicity is possible based on its mechanism of action

Infusion reactions

• Infusion-related reactions, including severe and life-threatening reactions, reported
• Monitor for signs and symptoms of infusion-related reactions (e.g., rigors, chills, wheezing, itching, flushing, rash, low blood pressure, hypoxemia, fever)
• Premedicate with an antihistamine and acetaminophen

Hepatotoxicity

• In combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 ALT and AST elevation
• Consider more frequent monitoring of liver enzymes as compared to when drugs are used as monotherapy
• Withhold combination therapy for moderate (Grade 2) hepatotoxicity and permanently discontinue for severe or life-threatening (Grade 3 or 4) hepatotoxicity
• Administer corticosteroids as needed

Cardiovascular effects

• In combination with axitinib, can cause severe and fatal cardiovascular events
• Consider baseline and periodic evaluations of left ventricular ejection fraction; monitor for signs and symptoms of cardiovascular events
• Optimize management of cardiovascular risk factors (e.g., high blood pressure, diabetes, dyslipidemia)
• Discontinue avelumab and axitinib for Grade 3-4 cardiovascular events
• Also, see Dosage Modifications

Immune-mediated adverse reactions

• Immune-mediated pneumonitis, including fatal cases; monitor for signs and symptoms of pneumonitis and evaluate patients with suspected pneumonitis with radiographic imaging
• Immune-mediated hepatitis, including fatal cases, reported; monitor liver function tests before initiating and periodically during treatment
• In combination with axitinib, can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 ALT and AST elevation; consider more frequent monitoring of liver enzymes
• Monitor for symptoms of immune-mediated colitis; administer systemic corticosteroids for grade 2 or higher colitis
• Immune-mediated adrenal insufficiency should be treated with corticosteroids as appropriate for the adrenal insufficiency; monitor for signs/symptoms of adrenal insufficiency during and after treatment
• Immune-mediated endocrinopathies (e.g., hypothyroidism, hyperthyroidism) reported; monitor thyroid function before initiating drug and during treatment; treat hypothyroidism with hormone-replacement therapy; initiate medical management for control of hyperthyroidism
• Immune-mediated nephritis and renal dysfunction reported; monitor for elevated serum creatinine before treatment and periodically during treatment
• Type 1 diabetes mellitus, including diabetic ketoacidosis, reported; monitor for hyperglycemia or other signs and symptoms of diabetes; may resume avelumab when metabolic control is achieved with insulin or antihyperglycemics
• For Grade 2 or greater immune-mediated adverse reactions, administer corticosteroids (initial dose of 1-2 mg/kg/day prednisone or equivalent, followed by a taper) for Grade 2 or greater nephritis until resolution

Pregnancy and Lactation

• Based on its mechanism of action, fetal harm may occur when avelumab is administered to a pregnant woman. Animal studies demonstrated that PD-1/PD-L1 pathway inhibition can lead to an increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death. Human IgG1 immunoglobulins (IgG1) are known to cross the placenta; therefore, the transmission may potentially occur from the mother to the developing fetus. The patient should be advised of the potential risk to a fetus.
• Females of reproductive potential are advised to use effective contraception during treatment with avelumab and for at least 1 month after the last dose.
• It is unknown if avelumab is distributed in human breast milk. Women are advised not to breastfeed during treatment with avelumab and for at least 1 month after the last dose, owing to the potential for serious adverse reactions in breastfed infants.