atezolizumab

a-te-zoe-LIZ-ue-mab

Therapeutic Classification: antineoplastics

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

High Alert

First-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients whose tumors have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥ 10% of the tumor area) and have no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations (as monotherapy).
Metastatic NSCLC in patients who have disease progression during or following platinum-containing chemotherapy (as monotherapy). Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab.
Stage II to IIIA NSCLC as adjuvant treatment following resection and platinum-based chemotherapy in patients whose tumors have PD-L1 expression on ≥ 1% of tumor cells (as monotherapy).
Metastatic non-squamous, NSCLC as first-line therapy in patients whose tumors have no EGFR or ALK genomic tumor aberrations (in combination with bevacizumab, paclitaxel, and carboplatin).
Metastatic nonsquamous NSCLC as first-line therapy in patients whose tumors have no EGFR or ALK genomic tumor aberrations (in combination with paclitaxel protein bound and carboplatin).
Extensive-stage small cell lung cancer as first-line therapy (in combination with carboplatin and etoposide).
Unresectable or metastatic hepatocellular carcinoma in patients who have not previously received systemic therapy (in combination with bevacizumab).
BRAF V600 mutation-positive unresectable or metastatic melanoma (in combination with cobimetinib and vemurafenib).
Unresectable or metastatic alveolar soft part sarcoma (as monotherapy).

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

Therapeutic effects:

Decreased spread of NSCLC, small cell lung cancer, hepatocellular carcinoma, and melanoma with increased survival.
Decreased spread of alveolar soft part sarcoma.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 27 days.

( plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Allogeneic hematopoietic stem cell transplant recipients (↑ risk of transplantation complications);
Solid organ transplant recipients (↑ risk of rejection);
Rep: Women of reproductive potential;
Pedi: Children <2 yr (alveolar soft part sarcoma) or <18 yr (all other indications) (safety and effectiveness not established).

CV: peripheral edema, myocarditis, pericarditis

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

Endo: hypothyroidism, ADRENAL INSUFFICIENCY, hyperglycemia, hyperthyroidism, hypophysitis, type 1 diabetes mellitus

F and E: hyponatremia, dehydration

GI: ↓appetite, colitis/diarrhea, constipation, hepatotoxicity, nausea, vomiting, ↑liver enzymes, abdominal pain, PANCREATITIS

GU: hematuria, ↓fertility (females), ↑serum creatinine, acute kidney injury, nephritis, urinary obstruction

Hemat: lymphopenia, anemia

Metab: hypoalbuminemia

MS: arthralgia

Neuro: Guillain-Barré syndrome, ENCEPHALITIS, MENINGITIS, MYASTHENIA GRAVIS, myelitis, nerve paresis

Resp: cough, dyspnea, INTERSTITIAL LUNG DISEASE

Misc: fatigue, fever, infection (including herpes encephalitis and tuberculosis), INFUSION-RELATED REACTIONS

Drug-drug:

None reported.

Non-Small Cell Lung Cancer

IV (Adults ): As monotherapy (metastatic NSCLC): 840 mg every 2 wk until disease progression or unacceptable toxicity or1200 mg every 3 wk until disease progression or unacceptable toxicity or1680 mg every 4 wk until disease progression or unacceptable toxicity. As monotherapy (adjuvant treatment): 840 mg every 2 wk for up to 1 yr unless there is disease recurrence or unacceptable toxicity or1200 mg every 3 wk for up to 1 yr unless there is disease recurrence or unacceptable toxicity or1680 mg every 4 wk for up to 1 yr unless there is disease recurrence or unacceptable toxicity. Combination therapy: 840 mg every 2 wk until disease progression or unacceptable toxicity or1200 mg every 3 wk until disease progression or unacceptable toxicity or1680 mg every 4 wk until disease progression or unacceptable toxicity. Administer prior to bevacizumab and chemotherapy when given on same day.

Small Cell Lung Cancer

IV (Adults ): 840 mg every 2 wk until disease progression or unacceptable toxicity or1200 mg every 3 wk until disease progression or unacceptable toxicity or1680 mg every 4 wk until disease progression or unacceptable toxicity. Administer prior to carboplatin and etoposide when given on same day.

Hepatocellular Carcinoma

IV (Adults ): 840 mg every 2 wk until disease progression or unacceptable toxicity or1200 mg every 3 wk until disease progression or unacceptable toxicity or1680 mg every 4 wk until disease progression or unacceptable toxicity. Administer prior to bevacizumab when given on same day.

Melanoma

IV (Adults ): 840 mg every 2 wk until disease progression or unacceptable toxicity or1200 mg every 3 wk until disease progression or unacceptable toxicity or1680 mg every 4 wk until disease progression or unacceptable toxicity. A 28-day treatment cycle of cobimetinib and vemurafenib should be administered prior to starting atezolizumab therapy.

Alveolar Soft Part Sarcoma

IV (Adults ): 840 mg every 2 wk until disease progression or unacceptable toxicity or1200 mg every 3 wk until disease progression or unacceptable toxicity or1680 mg every 4 wk until disease progression or unacceptable toxicity.
IV (Children ≥2 yr): 15 mg/kg (max dose = 1200 mg) every 3 wk until disease progression or unacceptable toxicity.

Solution for injection: 60 mg/mL

Monitor for signs and symptoms of pneumonitis (new or worsening cough, dyspnea, chest pain) during therapy. Monitor with x-rays as needed. For ≥Grade 2 pneumonitis, hold atezolizumab and administer corticosteroids at a dose of 1–2 mg/kg/day prednisolone equivalents followed by a taper. Resume after taper corticosteroid if Grade 0–1. If no complete or partial resolution within 12 wk of starting corticosteroids or inability to reduce prednisone to ≤10 mg per day within 12 wk of starting steroids, permanently discontinue atezolizumab. For Grade 3 or 4 pneumonitis, permanently discontinue atezolizumab.
Monitor for signs and symptoms of hepatitis (jaundice, severe nausea or vomiting, pain on right side of abdomen, lethargy, dark urine, unusual bleeding or bruising, anorexia) periodically during therapy.
Monitor for signs and symptoms of diarrhea or colitis (blood in stools, dark tarry stools, abdominal pain or tenderness) periodically during therapy. For Grade 2 or 3, hold atezolizumab until Grade 1 or resolved and corticosteroid dose ≤prednisone 10 mg per day (or equivalent). For Grade 4, permanently discontinue atezolizumab.
Monitor for signs and symptoms of adrenal insufficiency (extreme tiredness, dizziness or fainting, frequent urination, nausea or vomiting, changes in mood or behavior, ↓ sex drive, irritability, forgetfulness), hypophysitis (unusual headaches, persistent headaches, vision problems), hyperthyroidism, and type 1 diabetes periodically during therapy. If Grades 2, 3, or 4 occur, hold dose until Grade 1 or resolved and clinically stable on hormone replacement therapy.
Monitor for signs and symptoms of immune-mediated skin reactions (rash, pruritus, blistering, painful sores in mouth, nose, throat, genital area) periodically during therapy. Topical emollients and/or topical corticosteroids may treat mild to moderate nonexfoliative rashes. May cause exfoliative dermatitis (SJS, TEN, DRESS). If SJS, TEN, or DRESS is suspected, hold atezolizumab. If SJS, TEN, or DRESS are confirmed, permanently discontinue atezolizumab.
Monitor for signs and symptoms of meningitis or encephalitis (fever, confusion, changes in mood or behavior, extreme sensitivity to light, neck stiffness) during therapy. If symptoms occur, permanently discontinue atezolizumab. Administer 1–2 mg/kg/day methylprednisolone or equivalent. Convert to oral prednisone 60 mg/day or equivalent once improved. When symptoms improve to ≤ Grade 1, taper steroids over ≥1 mo.
Monitor for signs and symptoms of motor or sensory neuropathy (severe muscle weakness, numbness or tingling in hands or feet) periodically during therapy. For Grade 2 neurological toxicities, hold atezolizumab and administer corticosteroids at a dose of 1–2 mg/kg/day prednisolone equivalents followed by a taper. Resume after taper corticosteroid if Grade 0–1. If no complete or partial resolution within 12 wk of starting corticosteroids or inability to reduce prednisone to ≤10 mg per day within 12 wk of starting steroids, permanently discontinue atezolizumab. If Grades 3 or 4 or symptoms of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome occur, permanently discontinue atezolizumab. Institute treatment as needed.
Monitor for signs and symptoms of pancreatitis (abdominal pain) during therapy. If Grade 2 or 3 pancreatitis occurs, hold atezolizumab. Treat with methylprednisolone IV 1–2 mg/kg/day or equivalent. Once symptoms improve, follow with 1–2 mg/kg/day of oral prednisone or equivalent. Resume atezolizumab if symptoms of pancreatitis resolved and corticosteroid reduced to ≤10 mg/day oral prednisone or equivalent. For Grade 4 or recurrent pancreatitis, permanently discontinue atezolizumab.
Monitor for signs and symptoms of infection (fever, cough, frequent urination, flu-like symptoms, painful urination) periodically during therapy. Treat suspected or confirmed infections with antibiotics. For ≥Grade 3 or 4 infections, withhold atezolizumab until Grade 1 or resolved.
Monitor for signs and symptoms of infusion-related reactions (chills or shaking, itching or rash, flushing, dyspnea, wheezing, dizziness, fever, feeling faint, back or neck pain, facial swelling) during therapy. For Grade 1 or 2, interrupt or slow infusion. For Grade 3 or 4 infusion reactions, permanently discontinue atezolizumab.
Monitor for signs and symptoms of myocarditis (chest pain, irregular heartbeat, shortness of breath, swelling of ankles) during therapy. If Grade 2, 3, or 4 myocarditis occurs, discontinue atezolizumab permanently.

Lab Test Considerations:

Verify a negative pregnancy test before starting therapy.
- Confirm PD-L1 expression in melanoma via tests and BRAF V600 in unresectable or metastatic melanoma at http://www.fda.gov/CompanionDiagnostics. An FDA-approved test for the detection of other BRAF V600 mutations for this use is not currently available.
- For patients with hepatitis with no tumor involvement of the liver, monitor AST, ALT, and serum bilirubin prior to and periodically during therapy. If AST or ALT >3 and ≤ 8 times upper limit of normal (ULN) or total bilirubin >1.5 and ≤ 3 times ULN hold dose until Grade 1 or resolved and corticosteroid dose ≤prednisone 10 mg per day (or equivalent). If AST or ALT >8 times ULN or total bilirubin >3 times ULN, permanently discontinue atezolizumab. For patients with hepatitis with tumor involvement of the liver, If baseline AST or ALT >1 and ≤3 times ULN and increases to >5 and ≤10 times ULN or baseline AST or ALT >3 and ≤5 times ULN and increases to >8 and ≤10 times ULN, hold atezolizumab and administer corticosteroids at a dose of 1–2 mg/kg/day prednisolone equivalents followed by a taper. Resume after taper corticosteroid if Grade 0–1. If no complete or partial resolution within 12 wk of starting corticosteroids or inability to reduce prednisone to ≤10 mg per day within 12 wk of starting steroids, permanently discontinue atezolizumab. If AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN, permanently discontinue atezolizumab.
- Monitor thyroid function prior to and periodically during therapy. If asymptomatic, continue therapy. For symptomatic hypothyroidism (extreme tiredness, weight gain, constipation, feeling cold, hair loss, deepening voice), withhold atezolizumab and begin thyroid replacement therapy as needed without corticosteroids. For symptomatic hyperthyroidism (hunger, irritability, mood swings, weight loss), hold atezolizumab until Grade 1 or resolved and clinically stable on hormone replacement therapy. Resume therapy when symptoms of hyper- or hypothyroidism are controlled and thyroid function is improving.
- Monitor blood glucose periodically during therapy. For type 1 diabetes, begin treatment with insulin. For ≥Grade 2, 3, or 4 hyperglycemia (fasting glucose >250–500 mg/dL), hold atezolizumab until Grade 1 or resolved and control is achieved on insulin replacement therapy.
- Monitor serum amylase or lipase in patients with symptoms of pancreatitis. If serum amylase or lipase levels ≥Grade 3 (>2 times ULN), withhold atezolizumab. Treat with methylprednisolone IV 1–2 mg/kg/day or equivalent. Once symptoms improve, follow with 1–2 mg/kg/day of oral prednisone or equivalent. Resume atezolizumab if symptoms of pancreatitis resolved and corticosteroid ↓ to ≤10 mg/day oral prednisone or equivalent.
- Monitor renal function prior to and periodically during therapy. If serum creatinine increases to Grades 2 or 3, hold atezolizumab and administer corticosteroids at a dose of 1–2 mg/kg/day prednisolone equivalents followed by a taper. Resume after taper corticosteroid if Grade 0–1. If no complete or partial resolution within 12 wk of starting corticosteroids or inability to reduce prednisone to ≤10 mg per day within 12 wk of starting steroids, permanently discontinue atezolizumab. If serum creatinine increases to Grade 4, permanently discontinue atezolizumab.
- May cause lymphopenia, hyponatremia, anemia, ↑ alkaline phosphatase, ↑ serum creatinine, and hypoalbuminemia.

IV Administration:

Intermittent Infusion: Diluent: Dilute with 0.9% NaCl in a polyvinyl chloride, polyethylene, or polyolefin infusion bag. 3.2 mg/mL to 16.8 mg/mL. Gently invert to dilute; do not shake. Solution is clear and colorless to slightly yellow. Do not administer solutions that are discolored or contain particulate matter. Administer immediately once prepared or store for ≤6 hr at room temperature (including infusion time) or ≤24 hr if refrigerated. Do not freeze.
- Administer atezolizumab before chemotherapy or other antineoplastic drugs when given on same day.
Rate: Administer over 60 min with or without a sterile, nonpyrogenic, low-protein-binding in-line filter (0.2–0.22 micron); do not administer via IV push or bolus. If first infusion is tolerated, subsequent infusions may be infused over 30 min.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

Explain purpose of atezolizumab to patient. Advise patient to read the Medication Guide before starting and periodically during therapy in case of changes.
Advise patient to notify health care professional immediately if symptoms of pneumonitis, hepatitis, colitis, endocrine problems, meningitis, nervous system problems, ocular inflammatory toxicity (blurry or double vision, eye pain or redness), pancreatitis, infection, infusion-related reactions, or rash 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: May cause fetal harm. Advise females of reproductive potential to use effective contraception and to avoid breastfeeding during and for at least 5 mo after last dose. Inform females that atezolizumab may impair fertility during therapy.

Decreased spread of NSCLC, small cell lung cancer, hepatocellular carcinoma, and melanoma with increased survival.
Decreased spread of alveolar soft part sarcoma.

Tecentriq

NDC Code

12806- F. Hoffmann-La Roche AG
- 12806-0917-
  - 12806-0917-1- 120 L in 1 TANK (12806-0917-1)

12806- F. Hoffmann-La Roche AG
- 12806-0917-
  - 12806-0917-2- 300 L in 1 TANK (12806-0917-2)

50242- Genentech, Inc.
- 50242-917- TECENTRIQ
  - 50242-917-01- 1 VIAL, SINGLE-USE in 1 CARTON (50242-917-01) / 20 mL in 1 VIAL, SINGLE-USE

50242- Genentech, Inc.
- 50242-917- TECENTRIQ
  - 50242-917-86- 1 VIAL, SINGLE-USE in 1 CARTON (50242-917-86) / 20 mL in 1 VIAL, SINGLE-USE

50242- Genentech, Inc.
- 50242-918- TECENTRIQ
  - 50242-918-01- 1 VIAL, SINGLE-USE in 1 CARTON (50242-918-01) / 14 mL in 1 VIAL, SINGLE-USE

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