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Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.

durvalumab

( dur-VAL-ue-mab )
Funding:
New Drug Funding Program
  • Durvalumab - Locally Advanced Unresectable Stage III Non-Small Cell Lung Cancer Following Concurrent Chemoradiation
  • Durvalumab - In Combination with Etoposide and Platinum for Extensive-Stage Small Cell Lung Cancer
Other Name(s): Imfinzi®
Appearance: solution mixed into larger bags of fluids
A - Drug Name

durvalumab

COMMON TRADE NAME(S):   Imfinzi®

 
B - Mechanism of Action and Pharmacokinetics

Durvalumab is a fully human, high-affinity, immunoglobulin G1 kappa (IgG1K) monoclonal antibody that selectively blocks the PD-L1 interaction with PD-1 and CD-80 (B7.1) while leaving the PD-1/PD-L2 interaction intact. This selective blockade enhances antitumour immune responses that may be related to increased T-cell activation. Durvalumab does not induce antibody dependent cell-mediated cytotoxicity (ADCC).



Absorption
Time to reach steady state

approx. 16 weeks


Metabolism

Monoclonal antibodies are catabolised into peptides and amino acids.

Elimination
Half-life

18 days (terminal)

 
C - Indications and Status
Health Canada Approvals:

  • Urothelial carcinoma
  • Non-small cell lung cancer (NSCLC)
  • Small cell lung cancer (SCLC)

(Includes conditional approvals)
Refer to the product monograph for a full list and details of approved indications.



 
D - Adverse Effects

Emetogenic Potential:  

Minimal

Extravasation Potential:   None

The following table lists adverse effects considered drug-related that occurred in ≥ 5% of patients in the durvalumab phase III NSCLC trial comparing durvalumab to placebo. Serious adverse events from other studies and post-marketing may also be included. Adverse effects marked with “†” were based on a pooled data set across multiple monotherapy studies in various tumour types.

ORGAN SITE SIDE EFFECT* (%) ONSET**
Cardiovascular Hypertension (6%) E
Myocarditis (rare) D
Dermatological Rash, pruritus (22%) (may be severe) E  D
Gastrointestinal Abdominal pain (10%) E
Anorexia (14%) E
Constipation (12%) E
Diarrhea (18%) (may be severe - 2% colitis†) E  D
Nausea, vomiting (14%) E
General Edema (8%) E
Fatigue (24%) E
Hematological Immune thrombocytopenic purpura (immune-mediated; rare) E  D
Hepatobiliary ↑ LFTs (6%) (may be severe - 2% hepatitis†) E  D
Pancreatitis (rare) E
Hypersensitivity Infusion related reaction (2%) † I
Infection Infection (26%) (may be severe) E
Metabolic / Endocrine Adrenal insufficiency (rare) E  D  L
Diabetes mellitus (type 1; rare) E  D
Hyperthyroidism (8%) E  D
Hypophysitis (rare) E  D
Hypothyroidism (12%) E  D
Thyroiditis (2%) E  D
Musculoskeletal Musculoskeletal pain (12%) E
Nervous System Encephalitis (rare) E
Headache (11%) E
Insomnia (10%) E
Meningitis (aseptic; rare) E
Myasthenia gravis (rare) E
Myositis (rare) E  D
Ophthalmic Uveitis (rare) E
Renal Creatinine increased (5%) (may be severe - nephritis (rare)) E  D
Respiratory Cough, dyspnea (40%) (1% severe) E
Dysphonia (4%) E
Pneumonitis (3%) † (NSCLC: 34 % (3% severe), including radiation pneumonitis and interstitial lung disease) 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 durvalumab include infection, fatigue, rash, pruritus, diarrhea, anorexia, nausea/vomiting, constipation, hypothyroidism, musculoskeletal pain, and cough/dyspnea.

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.

Immune-mediated reactions, including pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, neuropathies and rash, have been reported and may be severe or fatal.

Rare cases of other significant immune-related toxicities have been reported with durvalumab or other PD-L1 inhibitors: Stevens-Johnson Syndrome, toxic epidermal necrolysis, rhabdomyolysis, encephalitis, demyelinating polyneuropathy, autoimmune hemolytic anemia and Guillain-Barré syndrome.

Both immune-mediated and radiation pneumonitis occurred more frequently in patients with locally advanced unresectable NSCLC who were treated with durvalumab within 6 weeks of chemoradiation compared to those who received placebo. The median time to onset was 55 days (range: 1-406 days).

Severe infections occurred in patients receiving durvalumab (some fatal). The most common grade 3 or 4 infections were urinary tract infections (urothelial carcinoma study) and pneumonia (NSCLC study). The overall incidence of infections was higher in a NSCLC study, compared to patients in other studies in whom radiation therapy was typically not administered immediately prior to durvalumab.

 
E - Dosing

Refer to protocol by which the patient is being treated.

Avoid the use of corticosteroids or immunosuppressants before starting treatment.

Consider pre-medication in patients with prior infusion related reactions. 



Adults:

Monotherapy:

Durvalumab 10 mg/kg IV every 2 weeks

OR

Durvalumab 1500 mg IV every 4 weeks

Patients with weight ≤ 30 kg must receive 10mg/kg every 2 weeks weight-based dosing, until weight increases to > 30 kg.

(For dosing in durvalumab maintenance (SCLC), refer to the DURV(MNT) regimen monograph.)


Combination therapy:

Dosing schedules depend on the indication. Refer to the product monograph or related regimen monograph(s) for details.


Dosage with Toxicity:

  • Healthcare professionals should also consult the most recent durvalumab product monograph for additional information.
  • Dose reductions are not recommended for durvalumab . Doses may be delayed or discontinued based on toxicity.

  • Hold durvalumab for severe infections; manage symptoms and treat with anti-infectives.

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.

 

Management of Infusion related Reactions

Severity Action
Grade 1 or 2

Interrupt or slow the rate of infusion by 50%.

Consider pre-medications prior to subsequent infusions.

Grade 3 or 4 Discontinue


Dosage with Hepatic Impairment:

Hepatic impairment Durvalumab dose
Mild (bilirubin ≤ ULN and AST > ULN or bilirubin >1 to ≤1.5 x ULN and any AST) No dosage adjustment is required

Moderate (total bilirubin > 1.5 - ≤3 x ULN and any AST) or Severe (total bilirubin > 3 x ULN and any AST)

No data

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



Dosage with Renal Impairment:

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

Renal impairment Durvalumab dose
Mild to Moderate (CrCl ≥ 30 ml/min) No dosage adjustment is required
Severe (CrCl < 30 ml/min) No data 


Dosage in the elderly:

No dosage adjustment is required for patients aged 65 and older. 



Children:

Safety and efficacy has not been established in pediatric patients. 



 
F - Administration Guidelines
  • Administer by IV infusion over 60 minutes using a sterile, low-protein binding 0.2-0.22 micron in-line filter.

  • Give durvalumab prior to chemotherapy when both are given on the same day.
  • Durvalumab is supplied as a single-use, preservative-free vial.

  • Visually inspect the vial for particulates and discolouration prior to dilution. Undiluted solution should be clear to opalescent and colorless to slightly yellow.

  • Using aseptic technique, withdraw the required drug volume and transfer to an IV bag of NS or D5W to a final concentration of 1 to 15 mg/mL.

  • Mix by gentle inversion; do not shake.

  • Do not co-administer with other drugs; flush line after each dose.

  • Store unused drug vials under refrigeration (2-8oC) in the original package.
  • Protect from light and do not freeze.
 
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.

  • Some clinical trials excluded patients with a history of immunodeficiency; medical conditions that required systemic immunosuppression; history of severe immune-mediated adverse reactions; history of allogeneic organ transplantation; untreated CNS metastases; HIV; active tuberculosis, hepatitis B or C infection, or patients who received live attenuated vaccine(s) within 30 days before or after starting durvalumab.

  • Use caution when driving or operating machinery, as patients may experience adverse effects affecting their ability to concentrate or react.

 


Other Drug Properties:

  • Carcinogenicity: Unknown

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

    Durvalumab 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 3 months after the last dose.

  • Excretion into breast milk: Likely

    Immunoglobulins are known to be secreted into breast milk; therefore as a human IgG1k antibody, there is potential for infant exposure to durvalumab via breast milk.

    Breastfeeding is not recommended during treatment and for at least 3 months after the last dose. 

  • Fertility effects: Unknown
 
H - Interactions

No formal pharmacokinetic drug-drug interaction studies have been conducted. 

Use of systemic corticosteroids or immunosuppressants should be avoided prior to starting durvalumab because of potential interference with efficacy. They can be used to treat immune-mediated reactions after starting the drug. Corticosteroids may be used as premedication (e.g. antiemetic) when given with chemotherapy.

 
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; more frequent with severe toxicity

Renal function tests

Baseline, before each dose, and as clinically indicated; more frequent with severe toxicity

Thyroid function tests

Baseline and before each dose or at least once per month

Blood glucose

Baseline, before each dose, and as clinically indicated

Clinical toxicity assessment for infection, fatigue, infusion reactions, immune-mediated reactions, including GI, skin, ocular, respiratory, neurologic, cardiac, musculoskeletal, and endocrine toxicities

At each visit and as clinically indicated

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



 
J - Supplementary Public Funding

New Drug Funding Program (NDFP Website )

  • Durvalumab - Locally Advanced Unresectable Stage III Non-Small Cell Lung Cancer Following Concurrent Chemoradiation
  • Durvalumab - In Combination with Etoposide and Platinum for Extensive-Stage Small Cell Lung Cancer

 
K - References

Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018. DOI: 10.1056/NEJMoa1809697

Durvalumab (Imfinzi®) product monograph. AstraZeneca Canada Inc., April 2022.

Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet . 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6

Powles T, O'Donnell PH, Massard C, et al. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411.


July 2022 added NDFP form

 
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.