durvalumab

High Alert

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).
Resectable (tumors≥4 cm and/or node positive) NSCLC with no known EGFR mutations or ALK rearrangements (in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by monotherapy as adjuvant treatment after surgery).
First-line treatment of extensive-stage small cell lung cancer (in combination with etoposide and either carboplatin or cisplatin).
Limited-stage small cell lung cancer in patients whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.
Locally advanced or metastatic biliary tract cancer (in combination with gemcitabine and cisplatin).
Unresectable hepatocellular carcinoma (in combination with tremelimumab).
Primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) (in combination with carboplatin and paclitaxel followed by monotherapy).
Muscle invasive bladder cancer (in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent durvalumab as adjuvant treatment following radical cystectomy).

Action ⬆ ⬇

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 small cell lung cancer, biliary tract cancer, hepatocellular carcinoma, and bladder cancer.
Improved progression-free survival in endometrial cancer.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 18 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

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

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, MYOCARDITIS, pericarditis, vasculitis

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

EENT: keratitis, uveitis

Endo: hyperglycemia, immune-mediated hypothyroidism, immune-mediated adrenal insufficiency, immune-mediated hyperthyroidism, immune-mediated hypophysitis, 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: fatigue, autoimmune neuropathy, ENCEPHALITIS, Guillain-Barré syndrome, MENINGITIS, myasthenic syndrome, myelitis

Resp: cough, dyspnea, immune-mediated pneumonitis

Misc: fever, infection, INFUSION-RELATED REACTIONS

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

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; continue until disease progression, unacceptable toxicity, or a maximum of 12 mo.

Metastatic Non-Small Cell Lung Cancer

IV (Adults ≥30 kg): Nonsquamous: 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): Nonsquamous: 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.

Neoadjuvant and Adjuvant Treatment of Resectable Non-Small Cell Lung Cancer

IV (Adults ≥30 kg): Neoadjuvant therapy: 1500 mg every 3 wk (administered prior to platinum-containing chemotherapy); continue for up to 4 cycles prior to surgery. Adjuvant therapy: 1500 mg every 4 wk (as monotherapy); continue for up to 12 cycles after surgery.
IV (Adults <30 kg): Neoadjuvant therapy: 20 mg/kg every 3 wk (administered prior to platinum-containing chemotherapy); continue for up to 4 cycles prior to surgery. Adjuvant therapy: 20 mg/kg every 4 wk (as monotherapy); continue for up to 12 cycles after surgery.

Extensive-Stage 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.

Limited-Stage Small Cell Lung Cancer

IV (Adults ≥30 kg): 1500 mg every 4 wk; continue until disease progression, unacceptable toxicity, or a maximum of 24 mo.
IV (Adults <30 kg): 20 mg/kg every 4 wk; continue until disease progression, unacceptable toxicity, or a maximum of 24 mo.

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.

dMMR Endometrial Cancer

IV (Adults ≥30 kg): 1120 mg every 3 wk for 6 cycles (administered prior to carboplatin and paclitaxel on the same day); then 1500 mg every 4 wk as monotherapy; continue until disease progression or unacceptable toxicity.
IV (Adults <30 kg): 15 mg/kg every 3 wk for 6 cycles (administered prior to carboplatin and paclitaxel on the same day); then 20 mg/kg every 4 wk as monotherapy; continue until disease progression or unacceptable toxicity.

Muscle Invasive Bladder Cancer

IV (Adults ≥30 kg): Neoadjuvant therapy: 1500 mg every 3 wk (administered prior to gemcitabine and cisplatin); continue for 4 cycles prior to surgery. Adjuvant therapy: 1500 mg every 4 wk (as monotherapy); continue for up to 8 cycles after surgery.
IV (Adults <30 kg): Neoadjuvant therapy: 20 mg/kg every 3 wk (administered prior to gemcitabine and cisplatin); continue for 4 cycles prior to surgery. Adjuvant therapy: 20 mg/kg every 4 wk (as monotherapy); continue for up to 8 cycles after surgery.

Availability ⬆ ⬇

Solution for injection: 50 mg/mL

Assessment ⬆ ⬇

Monitor for signs and symptoms of pneumonitis (new or worsening cough, chest pain, dyspnea). If Grade 2 pneumonitis occurs, hold durvalumab and administer prednisone 1–2 mg/kg/day (or equivalent); resume durvalumab when pneumonitis is Grade ≤1 after corticosteroid taper over ≥1 mo. If no partial or complete resolution occurs 12 wk after corticosteroid initiation, inability to ↓ dose to ≤10 mg prednisone equivalent per day within 12 wk of corticosteroid initiation when part of tremelimumab containing regimen, or for Grade 3 or 4 pneumonitis, permanently discontinue durvalumab.
Assess for signs and symptoms of colitis (diarrhea, severe abdominal pain, bloody or tarry stools) and intestinal perforation. If Grade 2 or 3 colitis occurs, hold durvalumab and administer prednisone 1–2 mg/kg/day (or equivalent); resume durvalumab when colitis is Grade ≤1 after corticosteroid taper over ≥1 mo. For Grade 3 when part of tremelimumab containing regimen, Grade 4 colitis, or any Grade perforation, permanently discontinue durvalumab.
Monitor for signs and symptoms of adrenal insufficiency, diabetes, hyperthyroidism, hypothyroidism, and hypophysitis periodically. If Grade 3–4 symptoms occur, hold durvalumab and treat as clinically indicated until stable or permanently discontinue durvalumab depending on severity.
Assess for rash periodically during therapy. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. If SJS, TEN, or DRESS suspected, hold durvalumab and initiate prednisone 1–2 mg/kg/day (or equivalent) followed by taper, until Grade ≤1 and ≤10 mg/day of prednisone (or equivalent) within 12 wk of corticosteroid initiation when part of tremelimumab containing regimen. If SJS, TEN, or DRESS confirmed, permanently discontinue durvalumab.
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, hold durvalumab until clinically stable.
Monitor for signs and symptoms of infusion-related reactions (fever, chills, flushing, itching or rash, dizziness, dyspnea, wheezing, back pain, neck pain, feeling faint, facial swelling). For Grade 1 or 2 infusion-related reactions when part of tremelimumab containing regimen, hold or slow rate of infusion. For Grade 3 or 4 infusion-related reactions when part of tremelimumab containing regimen, stop infusion and permanently discontinue durvalumab.
Monitor for other immune-mediated reactions (aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, myositis, uveitis, keratitis). For Grade 2 immune-mediated reactions, exclude other causes and initiate corticosteroids as indicated. For Grade 3 or 4 immune-mediated reactions, administer prednisone 1–4 mg/kg/day (or equivalent), followed by taper. Hold or permanently discontinue durvalumab for severe reaction.
Monitor for signs and symptoms of myocarditis (chest pain, irregular heartbeats, shortness of breath, swelling of ankles). If Grade 2, 3, or 4 myocarditis occurs when part of tremelimumab containing regimen, permanently discontinue durvalumab.
Monitor for signs and symptoms of neurological toxicities (meningitis, encephalitis, myelitis, myasthenic syndrome/myasthenia gravis including exacerbation, Guillain-Barré syndrome, nerve paresis, neuropathy). If Grade 2 neurological toxicities occur when part of tremelimumab containing regimen, hold durvalumab and begin prednisone 1–2 mg/kg/day (or equivalent) until Grade ≤1; then initiate corticosteroid taper over ≥1 mo. If Grade 3 or 4 neurological toxicities occur, permanently discontinue durvalumab.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Select patients for treatment of endometrial cancer based on presence of dMMR in tumor specimen. FDA-approved tests for dMMR status is available at https://www.fda.gov/companiondiagnostics.
- Monitor for signs and symptoms of hepatitis. In patients with no hepatic tumor involvement: For ALT or AST >3 but ≤8 times upper limit of normal (ULN) or total bilirubin >1.5 but ≤3 times ULN when part of tremelimumab containing regimen, hold durvalumab until Grade ≤1 and administer prednisone ≤10 mg/day (or equivalent). For ALT or AST >8 times ULN or total bilirubin >3 times ULN, permanently discontinue durvalumab. In patients with hepatic tumor involvement: If AST or ALT >1 but <3 times ULN at baseline and ↑ to >5 but <10 times ULN OR AST or ALT >3 but <5 times ULN at baseline and ↑ to >8 but <10 times ULN when part of tremelimumab containing regimen, hold dose and administer prednisone 1–2 mg/kg/day (or equivalent) until Grade ≤1; then initiate corticosteroid taper over ≥1 mo. If AST or ALT ↑ to >10 times ULN or total bilirubin ↑ to >3 times ULN, permanently discontinue durvalumab.
- Monitor thyroid function prior to and periodically during therapy.
- Monitor blood glucose periodically during therapy. May cause hypoglycemia.
- Monitor renal function prior to and during therapy. Initiate prednisone 1–2 mg/kg/day (or equivalent) for Grade 2–4 nephritis, followed by taper. If Grade 2 or 3 ↑ serum creatinine occurs when part of tremelimumab containing regimen, hold durvalumab until Grade ≤1 and ≤10 mg/day of prednisone (or equivalent) needed. If Grade 4 ↑ serum creatinine occurs, permanently discontinue durvalumab.
- May cause hypocalcemia, hyponatremia, and hyperkalemia.

Implementation ⬆ ⬇

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 particulates. Concentration: 1–15 mg/mL. Administer immediately after preparation. May be stored for up to 28 hr in refrigerator 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 same IV line.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider immediately if signs and symptoms of pneumonitis, hepatitis (jaundice, severe nausea or vomiting, pain on right side of abdomen, lethargy, easy bruising or bleeding, dark urine, light-colored stools), colitis, adrenal insufficiency (prolonged or unusual headache, feeling cold, extreme tiredness, constipation, weight gain or loss, deepening voice, dizziness or fainting, ↑ urination , ↑ hunger or thirst, nausea or vomiting, hair loss, abdominal pain, changes in mood or behavior, ↓ sex drive, irritability, forgetfulness), nephritis (↓ urine output, hematuria, ankle edema, loss of appetite, rash, itching, skin blistering), or infusion-related reactions occur.
Advise patient to inform health care provider if neck stiffness, fatigue, excessive bleeding or bruising, confusion, muscle weakness or pain, fever, vision changes, chest pain, shortness of breath, irregular heartbeat, eye pain or redness, or mood or behavior changes occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception and avoid breastfeeding during therapy and for ≥3 mo after last dose. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇