You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search

COVID-19: Get the latest updates or take a self-assessment.

Chemotherapy and other systemic treatment regimens may change due to COVID-19. Find out more at Systemic Treatment Regimens During COVID-19.

avelumab

( a VEL ue mab )
Funding:
New Drug Funding Program
  • Avelumab - Metastatic Merkel Cell Carcinoma
Other Name(s): Bavencio(TM)
Appearance: solution mixed into larger bags of fluids
A - Drug Name

avelumab

COMMON TRADE NAME(S):   Bavencio(TM)

 
B - Mechanism of Action and Pharmacokinetics

Avelumab is a fully human monoclonal antibody (IgG1) that inhibits the suppressive effects of PD-L1 on cytotoxic T cells, thereby restoring the anti-tumour immune response. 



Absorption
Time to reach steady state 4 to 6 weeks (2 to 3 cycles) when administered every 2 weeks

Distribution

Avelumab is distributed mainly in the systemic circulation, with less distribution to the extracellular space. 

Avelumab exposure increases proportionally to dose in the range of 10-20 mg/kg every 2 weeks. 

Metabolism

Monoclonal antibodies are degraded into small peptides and amino acids via catabolic pathways. 

Elimination
Half-life

(terminal) 6.1 days

 
C - Indications and Status
Health Canada Conditional Approvals
(pending the result of studies to verify the drug’s clinical benefit. Patients should be advised of the nature of the marketing authorization granted.)

For the treatment of metastatic Merkel cell carcinoma (MCC) in previously treated adults.*

For the treatment locally of advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-based chemotherapy.*

 

*Conditional approval was based on tumour response and durability of response. An improvement in survival or disease-related symptoms has not yet been established.



 
D - Adverse Effects

Emetogenic Potential:  

Minimal

Extravasation Potential:   None

The following table lists adverse effects that occurred in ≥ 1% of patients from the single arm study in locally advanced or metastatic UC receiving avelumab. It also includes severe, life-threatening and post-marketing adverse effects from other indications.

ORGAN SITE SIDE EFFECT* (%) ONSET**
Cardiovascular Hypertension (10%) E
Myocarditis (rare) E  D
Dermatological Rash, pruritus (15%) (may be severe) E
Gastrointestinal Abdominal pain (19%) E
Anorexia, weight loss (21%) E
Constipation (18%) E
Diarrhea (18%) (may be severe, 1.5% colitis) E
Nausea, vomiting (23%) E
General Edema (16%) E
Fatigue (40%) E
Hematological Anemia (19%) E  D
Hepatobiliary ↑ Amylase / lipase (15%) E
↑ LFTs (36%) 7% severe; 1% autoimmune hepatitis E  D
Hypersensitivity Hypersensitivity (1%) I  E
Infusion related reaction (23%) (may be severe) I  E
Immune Antibody response (4%) E  D
Metabolic / Endocrine Abnormal electrolyte(s) (37%) ↓Na, ↓K (15% severe)
Adrenal insufficiency (0.5%) E  D
Diabetes mellitus (type 1; rare) E  D
Hyperthyroidism (1%) E
Hypothyroidism (4%) E  D
Musculoskeletal Musculoskeletal pain (25%) E
Myositis (0.5%) E  D
Other - Rheumatoid arthritis (rare) E
Nervous System Guillain-Barre syndrome (rare) E
Ophthalmic Uveitis (rare) E
Renal Nephrotoxicity (16%) (nephritis - rare ) E  D
Respiratory Cough, dyspnea (17%) E
Pneumonitis (1%) E  D


* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days)     E = early (days to weeks)
D = delayed (weeks to months)      L = late (months to years)

The most common side effects for avelumab include fatigue, abnormal electrolyte(s), ↑ LFTs, musculoskeletal pain, infusion related reaction, nausea, vomiting, anorexia, weight loss, abdominal pain, anemia, constipation and diarrhea.

Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions of Immune-related toxicities and their management.

Presentation of immune-mediated reactions may be different compared to other anti-cancer agents and early diagnosis and appropriate management is critical.

Severe, including fatal cases of immune-mediated pneumonitis have been reported. The median time to development with avelumab was 11 weeks (range: 3 days to 11 months) and the median duration was 35 days (range: 4 days to >4 months).

Immune-mediated hepatotoxicity has been reported and may be severe or fatal. The median time to onset of immune-mediated hepatitis was 14 weeks (range: 1 week to 15 months). The median duration was 26 days (range: 1 day to 5 months).

Immune-mediated colitis has occurred. The median time to onset of colitis was 9 weeks (range: 2 days to 11 months) and the median duration was 26 days (range: 1 day to over 14 months). 

Immune-mediated endocrinopathies, including thyroid disorders, adrenal insufficiency and type 1 diabetes mellitus (including diabetic ketoacidosis) have been reported. The median time to onset of thyroid disorders was 12 weeks (range: 2 weeks to 13 months). The median duration was not estimable (range: 6 days to > 21 months).

Severe infusion related reactions have been reported.

Anti-drug antibodies have been reported, but did not appear to impact the risk of infusion-related reactions.

 
E - Dosing

Premedication with an antihistamine and acetaminophen prior to the first 4 infusions is recommended. Consider for subsequent infusions based on clinical judgement and prior infusion reactions. 

 



Adults:

Avelumab 10 mg/kg IV every 2 weeks until disease progression or unacceptable toxicity 


Dosage with Toxicity:

Healthcare professionals should also consult the most recent avelumab product monograph for additional information.

Dose reductions are not recommended for avelumab . Doses may be delayed or discontinued based on toxicity.

 

Summary of Principles of Management of Immune-Related Adverse Effects (irAEs):

  • Immune-related adverse effects (irAEs) are different in their presentation, onset and duration compared to conventional chemotherapy. Patient and provider education is essential.

  • Initial irAEs presentation can occur months after completion of treatment and affect multiple organs.

  • Dose escalation or reduction is not recommended.

  • If no other cause can be identified (such as infection), any new symptom should be considered immune-related and prompt treatment initiated.

  • Organ-specific system-based toxicity management is recommended.

Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions of Immune-related toxicities and their management.

 

Infusion-related reactions:

Toxicity Grade Action
1 Slow infusion rate by 50%
2 Interrupt infusion until ≤ grade 1; restart at 50% lower infusion rate.
≥3 Discontinue

 



Dosage with Hepatic Impairment:

Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions for immune-related hepatic toxicity management.

Hepatic impairment Avelumab dose
Mild (bilirubin ≤ ULN and AST > ULN OR bilirubin 1-1.5 x ULN) no change
 
Moderate (bilirubin 1.5-3 x ULN)
Severe (bilirubin > 3 x ULN) no data 


Dosage with Renal Impairment:

Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions for immune-related renal toxicity management.

Creatinine clearance (ml/min) Avelumab dose
≥ 60 no change
 
30-59 
15-29


Dosage in the elderly:

Metastatic Merkel Cell Carcinoma:
Differences in safety or efficacy between patients aged 65 and older compared to younger patients have not been evaluated

Locally Advanced or Metastatic Urothelial Carcinoma:
No overall differences in safety or efficacy were reported between elderly patients and younger patients



Children:

Safety and efficacy in pediatric patients have not been established. 



 
F - Administration Guidelines
  • DO NOT administer as an IV push or bolus

  • Dilute avelumab with 0.9% or 0.45% saline solution prior to infusion. It must not be mixed with other products or diluents.

  • Mix the diluted solution by gentle inversion; do not shake

  • Infuse over 60 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 micrometer in-line or add-on filter

  • Do not co-administer with other drugs through the same IV line; flush the line with 0.9% or 0.45% saline after administration

  • Avelumab is compatible with polyethylene, polypropylene and ethylene vinyl acetate infusion bags, glass bottles, polyvinyl chloride infusion sets and in-line filters with polyethersulfone membranes and pore sizes of 0.2 micrometer.
  • Avelumab vials should be stored at 2-8oC; do not freeze

  • Store in the original container and protect from light

 
G - Special Precautions
Contraindications:

  • Patients who have a hypersensitivity to this drug or any of its components

Other Warnings/Precautions:

  • Use with caution and monitor closely in patients with pre-existing conditions such as colitis, hepatic impairment, respiratory or endocrine disorders, such as hypo or hyperthyroidism or diabetes mellitus.

  • Avelumab may cause fatigue; patients should be advised not to drive or operating machinery/tools until they are sure of feeling well.


Other Drug Properties:

  • Carcinogenicity: Unknown

Pregnancy and Lactation:
  • Crosses placental barrier: Yes
  • Fetotoxicity: Likely

    Avelumab may cause fetal harm and is not recommended for use in pregnancy.  Adequate contraception should be used by both sexes during treatment, and for at least 1 month after the last dose.

  • Excretion into breast milk: Likely

    Breastfeeding is not recommended during treatment and for at least 1 month after the last dose. 

  • Fertility effects: Unknown
 
H - Interactions

No drug interaction studies have been conducted. 

 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Monitor Type Monitor Frequency

CBC

Baseline, before each dose and as clinically indicated

Liver function tests

Baseline, before each dose and as clinically indicated

Renal function tests

Baseline, periodically during treatment and as clinically indicated

Thyroid function tests

Baseline and before each dose, or at least once monthly
Clinical toxicity assessment for infusion-related reactions, and immune-mediated reactions, including GI, skin, respiratory, hepatic, renal, cardiac, ophthalmic and endocrine toxicities At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version



 
J - Supplementary Public Funding

New Drug Funding Program (NDFP Website )

  • Avelumab - Metastatic Merkel Cell Carcinoma

 
K - References

Avelumab (Bavencio®) product monograph, EMD Serono, May 2018.

Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016 Oct;17(10):1374-1385.


May 2019 Updated Indication, Adverse Effects and Dosage with Toxicity sections.

 
L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.