DESCRIPTION
MECHANISM OF ACTION
• Human IgG1 kappa antibody that binds to the PD-L1 ligand expressed on tumor cells and/or tumor infiltrating cells, which then blocks the interaction between the PD-L1 ligand and the PD-1 and B7.1 receptors
found on T cells and antigen-presenting cells.
• Blockade of the PD-1 pathway-mediated immune checkpoint overcomes immune escape mechanisms and enhances T-cell immune response, leading to T-cell activation and proliferation.
DISTRIBUTION
Mean volume of distribution is 5.6 L. Steady-state concentrations are achieved at 16 weeks.
INDICATIONS
1. FDA-approved for locally advanced or metastatic urothelial cancer with disease progression during or following platinum-based chemotherapy.
2. FDA-approved for locally advanced or metastatic urothelial cancer with disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-based chemotherapy.
3. FDA-approved for unresectable stage III NSCLC in which disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.
DOSAGE RANGE
1. Urothelial cancer: 10 mg/kg IV every 2 weeks.
2. NSCLC: 10 mg/kg IV every 2 weeks.
DRUG INTERACTIONS
None well characterized to date.
SPECIAL CONSIDERATIONS
1. Durvalumab can result in significant immune-mediated adverse reactions due to T-cell activation and proliferation. These immune-mediated reactions may involve any organ system, with the most common reactions being pneumonitis, enterocolitis, hepatitis, dermatitis, hypophysitis, nephritis, and thyroid dysfunction.
2. Mild hepatic impairment does not affect durvalumab pharmacokinetics. However, the effect of moderate or severe hepatic impairment on drug metabolism has not been well characterized.
3. Mild-to-moderate renal impairment does not affect durvalumab pharmacokinetics. However, the effect of severe renal impairment on drug metabolism has not been well characterized.
4. Durvalumab should be withheld for any of the following:
• Grade 2 pneumonitis
• Grade 2 colitis
• SGOT/SGPT > 3-5 × ULN or total bilirubin > 1.5-3 × ULN
• Serum creatinine > 1.5-3 × ULN
• Any other severe or grade 3 treatment-related toxicity
5. Durvalumab should be permanently discontinued for any of the following:
• Any life-threatening or grade 4 toxicity
• Grade 3 or 4 pneumonitis
• Grade 3 or 4 colitis
• SGOT/SGPT > 8 × ULN or total bilirubin > 5 × ULN
• Serum creatinine > 3-6 × ULN
6. Monitor thyroid and adrenal function prior to and during therapy.
7. Immune-mediated reactions may occur even after discontinuation of therapy.
8. Durvalumab can cause fetal harm, and women should use effective contraception while on therapy and for at least 3 months following the last dose of therapy.
9. Breastfeeding is not recommended during therapy and for at least 3 months after the last dose of therapy.
TOXICITY 1
Fatigue, anorexia, and asthenia.
TOXICITY 2
Pneumonitis with dyspnea and cough.
TOXICITY 3
Hepatitis with elevations in SGOT/SGPT and serum bilirubin.
TOXICITY 4
Colitis with diarrhea and abdominal pain.
TOXICITY 5
Endocrinopathies, which include hypothyroidism, hyperthyroidism, adrenal insufficiency, diabetes mellitus, and hypophysitis/hypopituitarism.
TOXICITY 6
Neurologic toxicity with neuropathy, myositis, myasthenia gravis, and Guillain-Barré syndrome.
TOXICITY 7
Renal toxicity with nephritis.
TOXICITY 8
Maculopapular skin rash, erythema, dermatitis, and pruritus.
TOXICITY 9
Infusion-related reactions.
TOXICITY 10
Musculoskeletal symptoms, which may present with arthralgias, oligoarthritis, polyarthritis, tenosynovitis, polymyalgia rheumatica, and myalgias.
SPECIFICATION
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