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
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 anti-tumour immune responses that may be related to increased T-cell activation. Durvalumab does not induce antibody dependent cell-mediated cytotoxicity (ADCC).
| Time to reach steady state | approx. 16 weeks |
Monoclonal antibodies are catabolized into peptides and amino acids.
| Half-life | 18 days (terminal) |
- Urothelial carcinoma
- Non-small cell lung cancer (NSCLC)
- Small cell lung cancer (SCLC)
- Biliary tract cancer
(Includes conditional approvals)
Refer to the product monograph for a full list and details of approved indications.
Emetogenic Potential:
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 | |||
| Stevens-Johnson syndrome (rare) | E | ||||
| Toxic epidermal necrolysis (rare) | E | ||||
| 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 | |||
| Rhabdomyolysis (rare) | E | ||||
| Nervous System | Encephalitis (rare) | E | |||
| Guillain-Barre syndrome (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, Guillain-Barré syndrome, and aplastic anemia.
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.
Refer to protocol by which the patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Avoid the use of corticosteroids or immunosuppressants before starting treatment.
Consider pre-medication in patients with prior infusion related reactions.
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, refer to the DURV(MNT) regimen monographs.)
Combination therapy:
Dosing schedules depend on the indication. Refer to the product monograph or related regimen monograph(s) for details.
- 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.
Non-immune-related toxicity
| Severity | Action |
| Grade 2 or 3 | Hold until ≤ Grade 1 or baseline |
| Grade 4 | Discontinue* |
*Decision to discontinue for lab abnormalities should be based on signs/ symptoms and clinical judgement.
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 |
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions for immune-related hepatitis management.
| 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 (bilirubin >1.5 to 3 x ULN and any AST) | |
Severe (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 nephritis management.
| Creatinine Clearance (mL/min) | Durvalumab Dose |
| ≥ 30 | No dosage adjustment is required |
| < 30 | No data |
No dosage adjustment is required for patients aged 65 and older. No overall differences in safety or efficacy were reported between patients ≥ 65 years of age and younger patients.
Safety and efficacy have not been established in pediatric patients.
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 unopened drug vials under refrigeration (2-8oC) in the original package.
Protect from light and do not freeze.
- 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 patients and their partners 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
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.
Acetaminophen may affect the response to immune checkpoint inhibitors. Further clinical studies are needed to determine the exact mechanism and the appropriate clinical management (Bessede et al, 2022).
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
| Monitor Type | Monitor Frequency |
|---|---|
CBC | Baseline and Q3-6 weeks, or as clinically indicated |
Liver function tests | Baseline and Q3-6 weeks, or as clinically indicated |
Serum creatinine, urine protein | Baseline and Q3-6 weeks, or as clinically indicated |
Thyroid function tests | Baseline, and as clinically indicated |
Blood glucose | Baseline, 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
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
- Durvalumab - Locally Advanced Unresectable or Metastatic Biliary Tract Cancer
- Durvalumab in combination with Tremelimumab - Previously Untreated Unresectable or Metastatic Hepatocellular Carcinoma (HCC)
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
Bessede A, Marabelle A, Guegan JP, et al. Impact of acetaminophen on the efficacy of immunotherapy in cancer patients. Ann Oncol 2022;33(9):909-15.
Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary cancer. NEJM Evidence. 2022 Jun 1:EVIDoa2200015.
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.
Product monograph: Durvalumab (Imfinzi®). AstraZeneca Canada Inc., December 2023.
April 2024 Modified Dosing with Toxicity section
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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