RX Patient Tools
Use these quick guides before reading the article, or return to them when you need help preparing questions for a doctor.
Avelumab is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). It is a fully human anti-PD immunoglobulin G1 (IgG1) lambda monoclonal antibody with antineoplastic actions. It was granted accelerated approval in March 2017 under the name Bavencio.
Mechanism of Action
PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. The binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen-presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation, and cytokine production. Avelumab binds PD-L1 through the FG loops 7 and blocks the interaction between PD-L1 and its receptors PD-1 and B7.1. This interaction releases the inhibitory effects of PD-L1 on the immune response resulting in the restoration of immune responses, including anti-tumor immune responses. Avelumab has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.
Indications
Avelumab is indicated for the treatment of adult and pediatric patients ≥12 years of age with metastatic Merkel cell carcinoma (MCC).
It is also indicated as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma (UC) which has not progressed with first-line platinum-containing chemotherapy. In addition, it is indicated in patients with locally advanced or metastatic UC who experience disease progression on or after platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Avelumab is additionally indicated as a first-line treatment, in combination with axitinib, in the treatment of advanced renal cell carcinoma (RCC).
Associated Conditions
- Advanced Renal Cell Carcinoma (RCC)
- Metastatic Urothelial Cancer
- Locally advanced Urothelial Carcinoma
- Metastatic Merkel Cell Carcinoma (MCC)
- First Line Chemotherapy
- Maintenance therapy
Avelumab is approved to treat
- Merkel cell carcinoma (a type of skin cancer) has spread. It is used in adults and children aged 12 years and older.
- Renal cell carcinoma (a type of kidney cancer) has spread or cannot be removed by surgery. It is used with axitinib as the first treatment.
- Urothelial cancer (a type of cancer in the bladder or urinary tract) that has spread or cannot be removed by surgery. It is used:
- As maintenance therapy in patients whose cancer did not get worse after first-line platinum chemotherapy.
- In patients whose cancer got worse during or after treatment with platinum chemotherapy.
This use is approved under FDA’s Accelerated Approval Program. As a condition of approval, confirmatory trial(s) must show that avelumab provides a clinical benefit in these patients.
Contraindications
- overactive thyroid gland
- a condition with low thyroid hormone levels
- low blood sugar
- decreased function of the adrenal gland
- a type of infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation of the lung called interstitial pneumonitis
- infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation of the large intestine
- kidney infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation
- abnormal liver function tests
- pregnancy
- a patient who is producing milk and breastfeeding
Dosage
Usual Adult Dose for Merkel Cell Carcinoma
- 800 mg IV over 60 minutes every 2 weeks
- Duration of therapy: Until disease progression or unacceptable toxicity
Usual Adult Dose for Urothelial Carcinoma
- 800 mg IV over 60 minutes every 2 weeks
- Duration of therapy: Until disease progression or unacceptable toxicity
Usual Adult Dose for Renal Cell Carcinoma
- 800 mg IV over 60 minutes every 2 weeks in combination with axitinib 5 mg orally 2 times a day (12 hours apart) with or without food
Duration of therapy: Until disease progression or unacceptable toxicity - Patients should be premedicated with an antihistamine and acetaminophen prior to the first 4 infusions; premedication should be administered for subsequent doses based on clinical judgment and the presence/severity of prior infusion reactions.
Usual Pediatric Dose for Merkel Cell Carcinoma
12 years and older:
- 800 mg IV over 60 minutes every 2 weeks
- Duration of therapy: Until disease progression or unacceptable toxicity
Renal Dose Adjustments
- Serum creatinine more than 1.5 and up to 6 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper
- Serum creatinine more than 6 x ULN: Permanently discontinue therapy.
Liver Dose Adjustments
- Aspartate aminotransferase (AST)/or alanine aminotransferase (ALT) more than 3 and up to 5 times the upper limit of normal (ULN) or total jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।" data-rx-term="bilirubin" data-rx-definition="Bilirubin is a yellow pigment that can build up in jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।">bilirubin more than 1.5 and up to 3 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of hepatitis after corticosteroid taper
- AST or ALT more than 5 x ULN or total jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।" data-rx-term="bilirubin" data-rx-definition="Bilirubin is a yellow pigment that can build up in jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।">bilirubin more than 3 X ULN: Permanently discontinue therapy.
Dosage Adjustments
DOSE ADJUSTMENTS FOR ADVERSE REACTIONS
PNEUMONITIS:
- Grade 2: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of pneumonitis after corticosteroid taper
- Grade 3 or 4 or recurrent Grade 2: Permanently discontinue therapy
HEPATITIS
- Aspartate aminotransferase (AST)/or alanine aminotransferase (ALT) more than 3 and up to 5 times the upper limit of normal (ULN) or total jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।" data-rx-term="bilirubin" data-rx-definition="Bilirubin is a yellow pigment that can build up in jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।">bilirubin more than 1.5 and up to 3 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of hepatitis after corticosteroid taper
- AST or ALT more than 5 x ULN or total jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।" data-rx-term="bilirubin" data-rx-definition="Bilirubin is a yellow pigment that can build up in jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।">bilirubin more than 3 X ULN: Permanently discontinue therapy
COLITIS
- Grade 2 or 3 diarrhea or colitis: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper
- Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis: Permanently discontinue therapy
ENDOCRINOPATHIES
- Endocrinopathies (including but not limited to hypothyroidism, hyperthyroidism, adrenal insufficiency, and hyperglycemia):
- Grade 3 or 4: Withhold therapy; administer corticosteroids as appropriate for adrenal insufficiency; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of endocrinopathies after corticosteroid taper
NEPHRITIS AND RENAL DYSFUNCTION:
- Serum creatinine more than 1.5 and up to 6 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper
- Serum creatinine more than 6 x ULN: Permanently discontinue therapy.
- For moderate or severe signs of an immune-mediated adverse reaction not previously described: Withhold therapy; administer high dose corticosteroids, and if appropriate, initiate hormone replacement; resume therapy in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper
- For any of the following: Life-threatening adverse reaction (excluding endocrinopathies); recurrent severe immune-mediated adverse reactions; requirement for 10 mg per day or greater prednisone or equivalent for more than 12 weeks; persistent Grade 2 or 3 immune-mediated adverse reactions lasting 12 weeks or longer: Permanently discontinue therapy
INFUSION-RELATED REACTIONS:
- Grade 1 or 2: Interrupt or slow the rate of infusion
- Grade 3 or 4: Permanently discontinue therapy
COMBINATION THERAPY
In patients with RCC being treated with this drug in combination with axitinib:
- If ALT or AST is 3 times the upper limit of normal (ULN) or greater but less than 5 x ULN or total bilirubin is 1.5 x ULN or greater but less than 3 x ULN: Withhold both this drug and axitinib until adverse reactions recover to Grade 0 or 1. If persistent (greater than 5 days), consider corticosteroid therapy (initial dose of 0.5 to 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. Dose reduction per the axitinib Full Prescribing Information if rechallenging with axitinib.
- If ALT or AST is 5 x ULN or greater or greater than 3 x ULN with concurrent total bilirubin 2 x ULN or greater or total bilirubin is 3 x ULN or greater, permanently discontinue both this drug and axitinib and consider corticosteroid therapy (initial dose 1 to 2 mg/kg/day prednisone or equivalent followed by a taper).
- When this drug is administered in combination with axitinib, review the axitinib Full Prescribing Information for recommended dose modifications for axitinib.
Administration advice:
- Do not freeze or shake the diluted solution.
- Administer the diluted solution over 60 minutes through an IV line containing a sterile, nonpyrogenic, low protein binding in-line filter (pore size of 0.2 microns).
- Do not coadminister other drugs through the same IV line
Reconstitution/preparation techniques:
- Visually inspect the vial for particulate matter and discoloration; it should be a clear, colorless to slightly yellow solution. Discard vial if the solution is cloudy, discolored, or contains particulate matter.
- Withdraw the required volume of drug from the vial(s) and inject it into a 250 mL infusion bag containing either 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection.
- Gently invert the bag to mix the diluted solution and avoid foaming or excessive shearing.
- Inspect the solution to ensure it is clear, colorless, and free of visible particles.
- Discard any partially used or empty vials.
Side effects
The Most Common
The most common serious adverse reactions to avelumab are immune-mediated
- adverse reactions (pneumonitis, hepatitis, colitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis) and life-threatening infusion reactions.
- Among the 88 patients enrolled in the JAVELIN Merkel 200 trial,
- the most common adverse reactions were fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema. Serious adverse reactions that occurred in more than one patient in the trial were acute kidney injury, anemia, abdominal pain, ileus, asthenia, and cellulitis.[rx][rx]
The most common serious risks are immune-mediated, where the body’s immune system attacks healthy cells or organs, such as the lungs (pneumonitis), liver (hepatitis), colon (colitis), hormone-producing glands (endocrinopathies) and kidneys (nephritis).[rxx] In addition, there is a risk of serious infusion-related reactions.[rx] Patients who experience severe or life-threatening infusion-related reactions should stop using avelumab.[rx] Women who are pregnant or breastfeeding should not take nivolumab because it may cause harm to a developing fetus or a newborn baby.[rx]
