Durvalumab

Indications

Durvalumab is used for: Indicated for locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy, or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, Patients w/ unresectable stage III, non-small cell lung cancer (NSCLC), whose disease has not progressed following platinum-based chemo- & radiation therapy.

Adult Dose

Adult 10 mg/kg IV infusion over 60 min every 2 wk until disease progression, unacceptable toxicity or max period: 12 mth.

Child Dose

Renal Dose

Administration

IV Preparation Withdraw the required volume for the dose from the vial(s) and transfer into an IV bag containing 0.9% NaCl or D5W Mix diluted solution by gentle inversion; do not shake the solution The final concentration of the diluted solution should be between 1-15 mg/mL Discard partially used or empty vials Administer infusion solution immediately once prepared (also see Storage) IV Administration Administer diluted solution via IV infusion over 1 hr through an IV line containing a sterile, low-protein binding 0.2 or 0.22 micron inline filter Do not co-administer other drugs through the same infusion line

Contra Indications

Precautions

Immune-mediated pneumonitis or interstitial lung disease reported; monitor for signs and symptoms; evaluate patients with suspected pneumonitis with radiographic imaging Administer corticosteroids, prednisone 1 to 2 mg per kg per day or equivalent for moderate (Grade 2) pneumonitis or prednisone 1 to 4 mg per kg per day or equivalent for more severe (Grade 3-4) pneumonitis, followed by taper; interrupt or permanently discontinue therapy based on the severity Immune-mediated hepatitis reported; monitor for abnormal liver tests each cycle during treatment Immune-mediated colitis or diarrhea reported; monitor for signs and symptoms Immune-mediated endocrinopathies (eg, hypothyroidism, hyperthyroidism, adrenal insufficiency, type 1 diabetes mellitus, hypophysitis, hypopituitarism) have occurred; monitor for symptoms of these conditions Rare reports of other immune-mediated adverse effects (eg, aseptic meningitis, hemolytic anemia, rash, ITP, myocarditis, myositis, nephritis, uveitis, keratitis) have occurred Severe infusion-related reactions reported; monitor for signs and symptoms and slow infusion rate or interrupt infusion if needed; if severe, withhold or permanently discontinue Can cause fetal harm Lactation Unknown if distributed in human breast milk; human IgG1 is excreted in human milk Durvalumab was present in the milk of lactating cynomolgus monkeys and was associated with premature neonatal death Because of the potential for adverse reactions in breastfed infants, advise breastfeeding women not to breastfeed during treatment and for at least 3 months after the last dose

Pregnancy-Lactation

Pregnancy Based on its mechanism of action, can cause fetal harm if administered to a pregnant woman Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery resulted in increased in premature delivery, fetal loss, and premature neonatal death Contraception: Advise females of reproductive potential to use effective contraception during treatment and for 3 months following the last dose Lactation Unknown if distributed in human breast milk; human IgG1 is excreted in human milk Durvalumab was present in the milk of lactating cynomolgus monkeys and was associated with premature neonatal death Because of the potential for adverse reactions in breastfed infants, advise breastfeeding women not to breastfeed during treatment and for at least 3 months after the last dose

Interactions

Durvalumab is an immunoglobulin, therefore no formal pharmacokinetic drug-drug interaction studies have been conducted with durvalumab.

Adverse Effects

Side effects of Durvalumab : >10% Adverse effects are for all grades unless otherwise specified Fatigue (39%) Infusion-related reactions (29.7%) Musculoskeletal pain (24%) Constipation (21%) Decreased appetite/hypophagia Nausea (16%) Peripheral edema (15%) Urinary tract infection (15%) Pyrexia/tumor associated fever (14%) Abdominal pain (14%) Dyspnea/exertional dyspnea (13%) Diarrhea/colitis (13%) Hyponatremia, grades 3-4 (12%) Lymphopenia, grades 3-4 (11%) Rash (11%) 1-10% Adverse effects are for all grades unless otherwise specified Cough (10%) Anemia, grades 3-4 (8%) Infusion-related reactions, grades 3-4 (6%) Increased alkaline phosphatase, grades 3-4 (4%) Hypermagnesemia, grades 3-4 (4%) Hypercalcemia, grades 3-4 (3%) Hyperglycemia, grades 3-4 (3%) Immune-mediated pneumonitis or ILD (2.3%) Increased AST, grades 3-4 (2%) Immune-mediated hepatitis (1.1%) Increased ALT, grades 3-4 (1%) Hyperbilirubinemia, grades 3-4 (1%) Increased creatinine, grades 3-4 (1%) Neutropenia, grades 3-4 (1%) Hyperkalemia, grades 3-4 (1%) Hypokalemia, grades 3-4 (1%) Hypoalbuminemia, grades 3-4 (1%) <1% Immune-mediated pneumonitis or ILD, grades 3-4 (0.4%)

Mechanism of Action

Human IgG1 kappa monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, and therefore overcoming/preventing PD-L1-mediated inhibition/suppression of T-cell activation Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity