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A - Regimen Name

AVEL Regimen
Avelumab


Disease Site
Skin - Merkel Cell

Intent
Palliative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses

For the treatment of metastatic Merkel cell carcinoma (MCC) in previously treated adults or adults ineligible for treatment with chemotherapy. 


Supplementary Public Funding

avelumab
New Drug Funding Program (Avelumab - Metastatic Merkel Cell Carcinoma) (NDFP Website )

 
B - Drug Regimen

avelumab
10 mg /kg IV Day 1
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C - Cycle Frequency

REPEAT EVERY 14 DAYS

Until disease progression or unacceptable toxicity

Note: NDFP funds a maximum of 12 months after confirmation of complete response.

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal

Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

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. 

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. 

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 irAE 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

 



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 

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

 

 


 
F - Adverse Effects

Refer to avelumab drug monograph(s) for additional details of adverse effects


Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • Fatigue
  • Abnormal electrolytes
  • ↑ LFTs
  • Musculoskeletal pain
  • Nausea, vomiting
  • Infusion related reaction (may be severe)
  • Anorexia, weight loss
  • Abdominal pain
  • Anemia
  • Constipation
  • Diarrhea
  • Cough, dyspnea
  • Edema
  • Nephrotoxicity
  • Rash, pruritus (may be severe)
  • ↑ Amylase / lipase
  • Hypertension
  • Immune related hypo/hyperthyroidism
  • Hypersensitivity
  • Adrenal insufficiency
  • Pneumonitis
  • Myocarditis
  • Immune related diabetes mellitus
  • Myositis
  • Rheumatoid arthritis
  • Guillain-Barre syndrome
  • Uveitis

 

 
G - Interactions

Refer to avelumab drug monograph(s) for additional details


No drug interaction studies have been conducted. 

 
H - Drug Administration and Special Precautions

Refer to avelumab drug monograph(s) for additional details


Administration

  • 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
     


Contraindications/Precautions
 

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


 

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.


 

Pregnancy / Lactation

  • 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.

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

  • Fertility effects: Unknown

 
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

  • 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


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K - References

Avelumab drug monograph, Cancer Care Ontario. 

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;17(10):1374-85.

June 2019 added link to antiemetic guideline


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. 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, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
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.