Usage
Durvalumab is prescribed for the treatment of various cancers, including:
- Non-Small Cell Lung Cancer (NSCLC): Specifically for unresectable, stage III NSCLC whose disease has not progressed after platinum-based chemotherapy and radiation therapy, and as neoadjuvant therapy, in combination with platinum-based chemotherapy followed by adjuvant durvalumab monotherapy after surgery, in adults with resectable (tumors ≥4 cm or node positive) NSCLC and no known EGFR mutations or ALK genetic changes.
- Small Cell Lung Cancer (SCLC): For extensive-stage SCLC in combination with etoposide and either carboplatin or cisplatin, and for adults with limited-stage SCLC (LS-SCLC) whose disease has not progressed after platinum-based chemotherapy and radiation therapy
- Urothelial Carcinoma: In certain locally advanced or metastatic settings.
- Biliary Tract Cancer: In combination with gemcitabine and cisplatin for advanced or metastatic disease that has not been previously treated.
- Hepatocellular carcinoma (HCC): For unresectable HCC in adults previously treated with sorafenib.
Pharmacological Classification: Durvalumab is a monoclonal antibody classified as an immune checkpoint inhibitor. More specifically, it is a programmed death-ligand 1 (PD-L1) blocking antibody.
Mechanism of Action: Durvalumab blocks the interaction between PD-L1 on tumor cells and PD-1 on T-cells. This blockade prevents the tumor from suppressing the immune response, allowing T-cells to recognize and attack cancer cells.
Alternate Names
International Nonproprietary Name (INN): Durvalumab
Brand Name: Imfinzi
How It Works
Pharmacodynamics: Durvalumab enhances the immune response against tumor cells by inhibiting the PD-1/PD-L1 pathway. This pathway is used by tumor cells to reduce the activation of T cells.
Pharmacokinetics:
- Absorption: Administered intravenously.
- Metabolism: The metabolism of durvalumab has not been fully characterized. As a human monoclonal antibody, it is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.
- Elimination: The clearance of durvalumab has not been found to be meaningfully impacted by concomitant chemotherapy treatment. No dose adjustments are needed based on weight, age, sex, race, mild to moderate renal impairment, or mild to moderate hepatic impairment. There are no data to determine dose adjustments for severe renal impairment or severe hepatic impairment.
Mode of Action: Durvalumab binds to PD-L1 expressed on tumor cells and in the tumor microenvironment, blocking its interaction with PD-1 on T-cells and CD80 (B7.1) on T-cells. This blockade removes the inhibitory signal on T-cells, allowing them to recognize and attack cancer cells more effectively.
Receptor Binding: Durvalumab binds specifically to the PD-L1 receptor.
Elimination Pathways: Primarily catabolic pathways, similar to endogenous IgG.
Dosage
Standard Dosage
Adults:
- NSCLC (unresectable, stage III): 10 mg/kg IV every 2 weeks or 1500 mg IV every 4 weeks until disease progression, unacceptable toxicity, or a maximum of 12 months (or 24 months for LS-SCLC).
- NSCLC (neoadjuvant/adjuvant): 1500 mg IV every 3 weeks for neoadjuvant therapy; 1500 mg IV every 4 weeks for adjuvant therapy.
- SCLC (extensive-stage): 1500 mg IV on Day 1 of each 21-day cycle for 4 cycles in combination with chemotherapy. Subsequent cycles: 1500 mg IV every 4 weeks.
- LS-SCLC: 1500 mg IV every 4 weeks for up to 24 months following concurrent chemoradiation.
Children: Limited data is available. Trials have investigated 15 mg/kg IV every 2 weeks. Safety and efficacy have not been fully established in pediatric patients.
Special Cases:
- Elderly Patients: No dose adjustment is required.
- Patients with Renal Impairment: No dose adjustment is required for mild or moderate impairment. Limited data for severe impairment.
- Patients with Hepatic Dysfunction: No dose adjustment is required for mild or moderate impairment. Limited data for severe impairment.
- Patients with Comorbid Conditions: Exercise caution in patients with pre-existing autoimmune conditions, immune deficiencies, or requiring systemic immunosuppression.
Clinical Use Cases
Durvalumab is not typically indicated for acute settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is primarily used as an anti-cancer agent in the outpatient setting.
Dosage Adjustments
Dose reductions are not recommended. Treatment may be withheld or discontinued based on toxicity.
Side Effects
Common Side Effects:
- Fatigue
- Cough
- Nausea
- Decreased appetite
- Upper respiratory tract infections
- Rash
- Diarrhea
- Musculoskeletal pain
Rare but Serious Side Effects:
- Pneumonitis (lung inflammation)
- Colitis (colon inflammation)
- Hepatitis (liver inflammation)
- Endocrine disorders (thyroid dysfunction, adrenal insufficiency, type 1 diabetes)
- Nephritis (kidney inflammation)
- Myocarditis (heart muscle inflammation)
- Neurological complications (Guillain-Barré syndrome, myasthenia gravis)
Long-Term Effects:
Long-term effects are still being studied, but potential complications may arise from immune-related adverse events.
Adverse Drug Reactions (ADR):
Any immune-mediated adverse event listed above can be a severe ADR requiring immediate medical attention and potentially corticosteroids.
Contraindications
- Hypersensitivity to durvalumab or any component of the formulation.
Drug Interactions
- Corticosteroids and Immunosuppressants: May interfere with durvalumab’s efficacy. Closely monitor patients.
- Live Vaccines: Avoid concomitant use due to the risk of infection.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Durvalumab can cause fetal harm and is contraindicated during pregnancy. Women of childbearing potential should use effective contraception during treatment and for at least 3 months after the last dose.
- Breastfeeding: Durvalumab may be present in breast milk. Breastfeeding is not recommended during treatment and for at least 3 months after the last dose.
Drug Profile Summary
- Mechanism of Action: PD-L1 blocking antibody; enhances anti-tumor immune response.
- Side Effects: Fatigue, cough, rash, diarrhea, pneumonitis, colitis, hepatitis, endocrine disorders.
- Contraindications: Hypersensitivity to durvalumab.
- Drug Interactions: Corticosteroids, immunosuppressants.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; not recommended while breastfeeding.
- Dosage: Variable depending on indication; usually 10 mg/kg IV every 2 weeks or 1500 mg IV every 4 weeks.
- Monitoring Parameters: Monitor for immune-related adverse events, including pulmonary, gastrointestinal, hepatic, endocrine, and renal function.
Popular Combinations
- Chemotherapy (e.g., etoposide, platinum agents) for SCLC and other cancers.
- Tremelimumab (another immune checkpoint inhibitor) in some settings like unresectable HCC.
Precautions
- General Precautions: Evaluate patients for pre-existing autoimmune conditions or other immune deficiencies.
- Specific Populations: See Pregnancy and Breastfeeding; monitor elderly patients as indicated by their general medical condition.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Durvalumab?
A: The dosage depends on the indication and patient factors. Common regimens include 10 mg/kg IV every 2 weeks or 1500 mg IV every 4 weeks.
Q2: How is Durvalumab administered?
A: Administered as an intravenous infusion over 60 minutes.
Q3: What are the most common side effects?
A: Fatigue, cough, rash, and diarrhea.
Q4: What are the serious side effects to watch out for?
A: Immune-related adverse events like pneumonitis, colitis, hepatitis, nephritis, and endocrine disorders.
Q5: Can Durvalumab be used during pregnancy or breastfeeding?
A: No, it is contraindicated during pregnancy and not recommended while breastfeeding.
Q6: What are the key drug interactions?
A: Concomitant use of corticosteroids or other immunosuppressants may reduce the effectiveness of durvalumab.
Q7: How does Durvalumab work against cancer?
A: It blocks PD-L1, an immune checkpoint protein, thereby activating the immune system to attack cancer cells.
Q8: How long is Durvalumab treatment typically given?
A: Until disease progression, unacceptable toxicity, or for a maximum of 12-24 months, depending on the indication and response.
Q9: What should be monitored during Durvalumab treatment?
A: Close monitoring of patients for immune-related adverse events is essential, with regular assessment of pulmonary, gastrointestinal, hepatic, endocrine, and renal function.
Q10: Are there any specific pre-treatment screening recommendations for Durvalumab?
A: Patients should be screened for pre-existing autoimmune conditions, immune deficiencies, or other comorbidities that may influence treatment decisions and management. This may include assessing thyroid function, liver function, and renal function.
Please note that this information is current as of February 16, 2025, and may change with evolving research and clinical practice.
