durvalumab

dur-VAL-ue-mab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, programmed death ligand 1 pd l1 inhibitors

REMS

Unresectable, stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed with concurrent platinum-containing chemotherapy and radiation.
Metastatic NSCLC in patients with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations (in combination with tremelimumab and platinum-based chemotherapy).
First-line treatment of extensive-stage small cell lung cancer (SCLC) (in combination with etoposide and either carboplatin or cisplatin).
Locally advanced or metastatic biliary tract cancer (in combination with gemcitabine and cisplatin).
Unresectable hepatocellular carcinoma (HCC) (in combination with tremilimumab).

Binds to programmed death ligand 1 (PD-L1) to prevent its interaction with the programmed cell death-1 (PD-1) and CD80 (B7.1) receptors, which activates the antitumor immune response.

Therapeutic effects:

Decreased spread of NSCLC with improved overall survival and progression-free survival.
Improved overall survival in SCLC, biliary tract cancer, and HCC.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 18 days.

(blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Allogeneic hematopoietic stem cell transplantation recipients (↑ risk for transplant-related complications);
Prior thoracic radiation (↑ risk of pneumonitis);
Rep: Woman of reproductive potential;
Pedi: Safety and effectiveness not established in children.

CV: peripheral edema, MYOCARDITIS, pericarditis, vasculitis

Derm: pruritus, rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: keratitis, uveitis

Endo: hyperglycemia, immune-mediated adrenal insufficiency, immune-mediated hyperthyroidism, immune-mediated hypophysitis, immune-mediated hypothyroidism, immune-mediated type 1 diabetes mellitus

F and E: hyperkalemia, hypocalcemia, hyponatremia, hypercalcemia, hypermagnesemia, hypokalemia

GI: ↓appetite, abdominal pain, constipation, nausea, gastritis, hypoalbuminemia, immune-mediated colitis, IMMUNE-MEDIATED HEPATITIS, pancreatitis

GU: immune-mediated nephritis

Hemat: lymphopenia, anemia, hemolytic anemia, NEUTROPENIA

MS: pain, myositis, RHABDOMYOLYSIS

Neuro: Guillain-Barré syndrome, autoimmune neuropathy, ENCEPHALITIS, MENINGITIS, myasthenic syndrome, myelitis

Resp: cough, dyspnea, IMMUNE-MEDIATED PNEUMONITIS

Misc: fatigue, fever, infection, INFUSION-RELATED REACTIONS

Drug-drug:

None reported.

Unresectable Stage III Non-Small Cell Lung Cancer

IV (Adults ≥30 kg): 10 mg/kg every 2 wk or 1500 mg every 4 wk; continue until disease progression, unacceptable toxicity, or a maximum of 12 mo.
IV (Adults <30 kg): 10 mg/kg every 2 wk until disease progression, unacceptable toxicity, or a maximum of 12 mo.

Metastatic Non-Small Cell Lung Cancer

IV (Adults ≥30 kg): Non-squamous: Cycles 1–4: 1500 mg on Day 1 every 3 wk (administered prior to platinum-based chemotherapy and following tremelimumab); Cycle 5 (3 wk after previous durvalumab dose): 1500 mg on Day 1 (administered prior to pemetrexed [if being used for maintenance]); Cycle 6 (4 wk after previous durvalumab dose): 1500 mg on Day 1 (administered prior to pemetrexed [if being used for maintenance] and following tremelimumab); Cycle 7 (4 wk after previous durvalumab dose) and beyond: 1500 mg on Day 1 every 4 wk (administered prior to pemetrexed [if being used for maintenance]); continue until disease progression or unacceptable toxicity. Squamous: Cycles 1–4: 1500 mg on Day 1 every 3 wk (administered prior to platinum-based chemotherapy and following tremelimumab); Cycle 5 (3 wk after previous durvalumab dose): 1500 mg on Day 1 (as monotherapy); Cycle 6 (4 wk after previous durvalumab dose): 1500 mg on Day 1 (administered following tremelimumab); Cycle 7 (4 wk after previous durvalumab dose) and beyond: 1500 mg on Day 1 every 4 wk (as monotherapy); continue until disease progression or unacceptable toxicity.
IV (Adults <30 kg): Non-squamous: Cycles 1–4: 20 mg/kg on Day 1 every 3 wk (administered prior to platinum-based chemotherapy and following tremelimumab); Cycle 5 (3 wk after previous durvalumab dose): 20 mg/kg on Day 1 (administered prior to pemetrexed [if being used for maintenance]); Cycle 6 (4 wk after previous durvalumab dose): 20 mg/kg on Day 1 (administered prior to pemetrexed [if being used for maintenance] and following tremelimumab); Cycle 7 (4 wk after previous durvalumab dose) and beyond: 20 mg/kg on Day 1 every 4 wk (administered prior to pemetrexed [if being used for maintenance]); continue until disease progression or unacceptable toxicity. Squamous: Cycles 1–4: 20 mg/kg on Day 1 every 3 wk (administered prior to platinum-based chemotherapy and following tremelimumab); Cycle 5 (3 wk after previous durvalumab dose): 20 mg/kg on Day 1 (as monotherapy); Cycle 6 (4 wk after previous durvalumab dose): 20 mg/kg on Day 1 (administered following tremelimumab); Cycle 7 (4 wk after previous durvalumab dose) and beyond: 20 mg/kg on Day 1 every 4 wk (as monotherapy); continue until disease progression or unacceptable toxicity.

Small Cell Lung Cancer

IV (Adults ≥30 kg): 1500 mg every 3 wk for 4 cycles (administered prior to etoposide and either carboplatin or cisplatin on the same day), then 1500 mg every 4 wk (as monotherapy); continue until disease progression or unacceptable toxicity.
IV (Adults <30 kg): 20 mg/kg every 3 wk for 4 cycles (administered prior to etoposide and either carboplatin or cisplatin on the same day), then 20 mg/kg every 4 wk (as monotherapy); continue until disease progression or unacceptable toxicity.

Biliary Tract Cancer

IV (Adults ≥30 kg): 1500 mg every 3 wk for up to 8 cycles (administered prior to gemcitabine and cisplatin on the same day), then 1500 mg every 4 wk (as monotherapy); continue until disease progression or unacceptable toxicity.
IV (Adults <30 kg): 20 mg/kg every 3 wk for up to 8 cycles (administered prior to gemcitabine and cisplatin on the same day), then 20 mg/kg every 4 wk (as monotherapy); continue until disease progression or unacceptable toxicity.

Hepatocellular Carcinoma

IV (Adults ≥30 kg): 1500 mg administered following a single dose of tremelimumab on Day 1 of Cycle 1, then 1500 mg every 4 wk (as monotherapy); continue until disease progression or unacceptable toxicity.
IV (Adults <30 kg): 20 mg/kg administered following a single dose of tremelimumab on Day 1 of Cycle 1, then 20 mg/kg every 4 wk (as monotherapy); continue until disease progression or unacceptable toxicity.

Solution for injection: 50 mg/mL

Monitor for signs and symptoms of pneumonitis (new or worsening cough, chest pain, shortness of breath). For Grade 2: hold dose and administer corticosteroids, prednisone 1 to 2 mg per kg per day or equivalent until ≤Grade 1. When ≤Grade 1, initiate corticosteroid taper and continue to taper over at least 1 mo. For Grade 3 or 4: permanently discontinue durvalumab.
Assess for signs and symptoms of colitis (diarrhea, severe abdominal pain, bloody or tarry stools) periodically during therapy. Initiate prednisone 1–2 mg/kg/day or equivalent, for moderate (Grade 2) or severe (Grade 3-4) colitis, followed by taper. If Grade 2 or 3 diarrhea or colitis occurs: hold dose until Grade 1 or resolved and corticosteroid dose ≤prednisone 10 mg per day (or equivalent). If Grade 4 diarrhea or colitis occurs: permanently discontinue durvalumab.
Monitor for signs and symptoms of adrenal insufficiency, diabetes, and hypophysitis periodically during therapy. Initiate prednisone 1 to 2 mg per kg per day or equivalent, for moderate (Grade 2) or severe (Grade 3-4) symptoms, followed by taper. If Grade 3–4 symptoms occur: hold durvalumab until clinically stable or permanently discontinue depending on severity.
Assess for rash periodically during therapy. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. May cause Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Initiate prednisone 1–2 mg/kg/day or equivalent, followed by taper. If SJS, TEN, or DRESS suspected, hold dose until Grade 1 or resolved and corticosteroid dose ≤ prednisone 10 mg per day (or equivalent). If SJS, TEN, or DRESS is confirmed, discontinue durvalumab permanently.
Monitor for signs and symptoms of infection (fever, cough, frequent urination, pain with urination, flu-like symptoms) prior to and periodically during therapy. If Grade 3 or 4 infection occurs: withhold dose until clinically stable.
Monitor for signs and symptoms of infusion-related reactions (pyrexia, chills, flushing, itching or rash, dizziness, dyspnea, wheezing, back pain, neck pain, feeling faint, facial swelling) during infusion. For Grade 1 or 2 infusion-related reactions: interrupt or slow rate of infusion. For Grade 3 or 4 infusion-related reactions: stop infusion and permanently discontinue durvalumab.
Monitor for other immune-mediated reactions (aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, myositis, and ocular inflammatory toxicity, including uveitis, keratitis). For Grade 2 immune-mediated adverse reactions: exclude other causes and initiate corticosteroids as indicated. For severe (Grade 3 or 4) adverse reactions: administer corticosteroids, prednisone 1 to 4 mg per kg per day or equivalent, followed by taper. Interrupt or permanently discontinue durvalumab for severe reaction.
Monitor for signs and symptoms of myocarditis (chest pain, irregular heartbeats, shortness of breath, swelling of ankles ) during therapy. If Grade 2, 3, or 4 myocarditis occurs, permanently discontinue durvalumab.
Monitor for signs and symptoms of neurological toxicities (meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis including exacerbation, Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy) during therapy. If Grade 2 toxicities occur, hold dose and begin corticosteroids, prednisone 1 to 2 mg per kg per day or equivalent until ≤Grade 1. When ≤Grade 1, initiate corticosteroid taper and continue to taper over at least 1 mo. If Grade 3 or 4 toxicities occur, permanently discontinue durvalumab.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.May cause immune-mediated hepatitis. Monitor for signs and symptoms of hepatitis. In patients with hepatitis with no tumor involvement of the liver, For ALT or AST >3 but ≤8 times upper limit of normal (ULN) or total bilirubin >1.5 but ≤3 times the ULN: hold dose until Grade 1 or resolved and corticosteroid dose ≤prednisone 10 mg per day (or equivalent). For ALT or AST >8 times ULN or total bilirubin >3 times ULN permanently discontinue durvalumab. In patients with hepatitis with tumor involvement of the liver,If AST or ALT >1 but <3 times ULN at baseline and increases to >5 but <10 times ULN or AST or ALT >3 <5 times ULN at baseline and increases to >8 but <10 times ULN, hold dose and administer corticosteroids, prednisone 1 to 2 mg per kg per day or equivalent until ≤Grade 1. When ≤Grade 1, initiate corticosteroid taper and continue to taper over at least 1 mo. If AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN, permanently discontinue durvalumab.
- Monitor serum thyroid prior to and periodically during therapy.
- Monitor blood glucose periodically during therapy.
- Monitor renal function prior to and periodically during therapy. Initiate prednisone 1–2 mg/kg/day or equivalent, for moderate (Grade 2) or severe (Grade 3-4) nephritis, followed by taper. For Grade 2 or 3 increases in serum creatinine, hold dose until Grade 1 or resolved and corticosteroid dose ≤ prednisone 10 mg per day (or equivalent). For Grade 4 increased serum creatinine, permanently discontinue durvalumab.
- May cause hypoglycemia, hypocalcemia, hyponatremia, and hyperkalemia.

Weigh patient before each infusion.

IV Administration:

Intermittent Infusion: Diluent: Dilute with 0.9% NaCl or D5W. Invert gently to mix; do not shake. Solution is clear to opalescent, colorless to slightly yellow. Do not administer solutions that are cloudy, discolored, or contain particulate matter. Concentration: 1 mg/mL to 15 mg/mL. Administer immediately after preparation. May be stored up to 28 hrs if refrigerated or up to 8 hr at room temperature. Do not freeze.
Rate: Administer over 60 min through a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.
Y-Site Incompatibility: Do not administer other drugs through the same infusion line.

Explain purpose of durvalumab to patient and family and inform of potential adverse reactions.
Advise patient to notify health are professional immediately if signs and symptoms of pneumonitis; hepatitis (jaundice, severe nausea or vomiting, pain on right side of abdomen, lethargy, or easy bruising or bleeding); colitis; adrenal insufficiency (prolonged or unusual headache, feeling cold, extreme tiredness, constipation, weight gain or weight loss, deepening voice, dizziness or fainting, urinating more often than usual, feeling more hungry or thirsty than usual, nausea or vomiting, hair loss, abdominal pain, changes in mood or behavior, decreased sex drive, irritability, forgetfulness); nephritis (decreased urine output, blood in urine, swelling in ankles, loss of appetite), rash, itching, or skin blistering; or infusion-related reactions occur.
Advise patient to inform health care professional if other signs and symptoms (neck stiffness; fatigue; excessive bleeding or bruising; confusion; muscle weakness or pain; fever; blurry vision, double vision, or other vision problem; chest pain, shortness of breath, irregular heartbeat; eye pain or redness; changes in mood or behavior) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 3 months after last dose of durvalumab.

Improved overall survival in SCLC, biliary tract cancer, and HCC.

Imfinzi

NDC Code

0310- AstraZeneca Pharmaceuticals LP
- 0310-4500- IMFINZI
  - 0310-4500-12- 1 VIAL in 1 CARTON (0310-4500-12) > 2.4 mL in 1 VIAL

0310- AstraZeneca Pharmaceuticals LP
- 0310-4611- IMFINZI
  - 0310-4611-50- 1 VIAL in 1 CARTON (0310-4611-50) > 10 mL in 1 VIAL

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