Introduction
Imfinzi (durvalumab) is a human monoclonal antibody classified as an immune checkpoint inhibitor. It is a programmed death-ligand 1 (PD-L1) blocking antibody developed by AstraZeneca. As an immunotherapy agent, Imfinzi represents a significant advancement in cancer treatment by harnessing the body's immune system to fight malignancies rather than directly targeting cancer cells.
Mechanism of Action
Imfinzi binds to PD-L1, a protein expressed on tumor cells and tumor-infiltrating immune cells. This binding blocks the interaction between PD-L1 and its receptors PD-1 and CD80 (B7.1). By inhibiting this pathway, Imfinzi releases the suppression of immune responses, including anti-tumor immune responses, without inducing antibody-dependent cell-mediated cytotoxicity (ADCC). This mechanism enables T-cells to recognize and attack tumor cells effectively.
Indications
Imfinzi is FDA-approved for the following indications:
1. Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC): For patients whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy 2. Extensive-Stage Small Cell Lung Cancer (ES-SCLC): In combination with etoposide and either carboplatin or cisplatin as first-line treatment 3. Locally Advanced or Metastatic Biliary Tract Cancer: In combination with gemcitabine and cisplatin 4. Hepatocellular Carcinoma (HCC): In combination with tremelimumab for patients who are not eligible for hepatic artery embolization
Dosage and Administration
Standard dosing: 10 mg/kg administered intravenously every 2 weeks or 1500 mg fixed dose every 4 weeks Administration:- Administer as an intravenous infusion over 60 minutes
- Do not administer as an intravenous push or bolus
- Premedication is not required
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary for mild to moderate impairment; use with caution in severe impairment
- Elderly patients: No dosage adjustment required
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Steady-state volume of distribution is approximately 6.3 L Metabolism: Expected to be degraded into small peptides and amino acids via catabolic pathways Elimination: Terminal half-life is approximately 18 days Clearance: Linear clearance with time-invariant pharmacokineticsContraindications
1. History of severe hypersensitivity to durvalumab or any of its excipients 2. No absolute contraindications based on organ function, but caution required in patients with certain autoimmune conditions
Warnings and Precautions
Immune-Mediated Adverse Reactions: Imfinzi can cause severe and fatal immune-mediated reactions including:- Pneumonitis
- Colitis
- Hepatitis
- Endocrinopathies (thyroid disorders, adrenal insufficiency, type 1 diabetes)
- Nephritis and renal dysfunction
- Dermatologic reactions
Drug Interactions
No formal drug interaction studies have been conducted. However, consider the following:
- Increased risk of immune-mediated adverse reactions when combined with other immunomodulatory drugs
- Potential for altered efficacy or toxicity when used with corticosteroids or other immunosuppressants
- Theoretical risk of reduced efficacy with concurrent strong immunosuppressive therapy
Adverse Effects
Most common adverse reactions (≥20%):- Fatigue (47%)
- Musculoskeletal pain (32%)
- Constipation (26%)
- Decreased appetite (22%)
- Nausea (22%)
- Rash (21%)
- Immune-mediated pneumonitis (3.4%)
- Immune-mediated hepatitis (2.8%)
- Immune-mediated colitis (1.8%)
- Severe infusion reactions (0.3%)
- Thyroid disorders (11%)
Monitoring Parameters
Baseline assessment:- Complete blood count with differential
- Comprehensive metabolic panel (including liver and renal function)
- Thyroid function tests
- Cortisol levels
- Pulmonary function assessment
- Monitor for signs and symptoms of immune-mediated adverse reactions
- Regular assessment of liver enzymes (ALT, AST, bilirubin)
- Thyroid function monitoring every 4-6 weeks
- Regular imaging to assess treatment response
- Monitor for infusion reactions during and after administration
Patient Education
Key points to discuss with patients:- Report any new or worsening symptoms immediately, especially:
- Shortness of breath or cough - Diarrhea or abdominal pain - Jaundice or dark urine - Excessive fatigue or weakness - Skin rash or itching - Fever or signs of infection
- Understand that immune-mediated reactions can occur even after treatment discontinuation
- Keep all scheduled follow-up appointments and laboratory tests
- Inform all healthcare providers about Imfinzi treatment
- Use effective contraception during treatment and for at least 3 months after final dose
References
1. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(20):1919-1929. 2. 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;394(10212):1929-1939. 3. Imfinzi [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2023. 4. FDA Approval: Durvalumab for Biliary Tract Cancer. Accessed from FDA.gov 5. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894-1905.