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Atezolizumab

Medically reviewed by Drugs.com. Last updated on Jul 18, 2020.

Pronunciation

(a te zoe LIZ ue mab)

Index Terms

  • Anti-PD-L1 Monoclonal Antibody MPDL3280A
  • MPDL3280A
  • RG7446
  • RO5541267

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Tecentriq: 840 mg/14 mL (14 mL); 1200 mg/20 mL (20 mL)

Brand Names: U.S.

  • Tecentriq

Pharmacologic Category

  • Antineoplastic Agent, Anti-PD-L1 Monoclonal Antibody
  • Antineoplastic Agent, Monoclonal Antibody

Pharmacology

Atezolizumab is a humanized monoclonal antibody immune checkpoint inhibitor that binds to programmed death ligand 1 (PD-L1) to selectively prevent the interaction between the programmed cell death-1 (PD-1) and B7.1 (also known as CD80) receptors, while still allowing interaction between PD-L2 and PD-1. PD-L1 is an immune check point protein expressed on tumor cells and tumor infiltrating cells and down regulates anti-tumor t-cell function by binding to PD-1 and B7.1; blocking PD-1 and B7.1 interactions restores antitumor t-cell function (Fehrenbacher 2016; Rosenberg 2016).

Immune checkpoint inhibition combined with the mitogen-activated protein kinase (MAPK) pathway increase antigen presentation and T-cell infiltration/activation to suppress tumor growth and improve tumor immunogenicity (when compared to targeted therapy alone).

Distribution

Vdss: 6.9 L

Excretion

Clearance: 0.2 L/day

Half-Life Elimination

27 days

Use: Labeled Indications

Breast cancer (triple negative), unresectable locally advanced or metastatic: Treatment of unresectable locally advanced or metastatic triple-negative breast cancer (in combination with paclitaxel [protein bound]) in adults whose tumors express programmed death-ligand 1 (PD-L1) (PD-L1 stained infiltrating immune cells [IC] of any intensity covering ≥1% of the tumor area) as determined by an approved test.

Hepatocellular carcinoma, unresectable or metastatic: Treatment of unresectable or metastatic hepatocellular carcinoma (in combination with bevacizumab) in patients who have not received prior systemic therapy.

Melanoma, unresectable or metastatic: Treatment of BRAF V600 mutation-positive unresectable or metastatic melanoma (in combination with cobimetinib and vemurafenib).

Non-small cell lung cancer, metastatic:

First-line treatment (single agent) of metastatic non-small cell lung cancer (NSCLC) in adults whose tumors have no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells [TC ≥50%] or PD-L1 stained tumor-infiltrating IC covering ≥10%), as determined by an approved test.

First-line treatment (in combination with bevacizumab, paclitaxel, and carboplatin) of metastatic non-squamous NSCLC in adults with no EGFR or ALK genomic tumor aberrations.

First-line treatment (in combination with paclitaxel [protein bound] and carboplatin) of metastatic NSCLC in adults with no EGFR or ALK genomic tumor aberrations.

Treatment (single agent) of metastatic NSCLC in adults with disease progression during or following platinum-containing chemotherapy (patients with EGFR or ALK genomic aberrations should have disease progression on approved therapy for EGFR or ALK genomic tumor mutations prior to receiving atezolizumab).

Small cell lung cancer, extensive stage: First-line treatment of extensive-stage small cell lung cancer in adults (in combination with carboplatin and etoposide).

Urothelial carcinoma, locally advanced or metastatic: Treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained infiltrating IC covering ≥5% of the tumor area) as determined by an approved test, in adults who are not eligible for any platinum-containing therapy regardless of PD-L1 status, or in adults who have disease progression during or following any platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy.

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to atezolizumab or any component of the formulation.

Dosing: Adult

Breast cancer (triple negative), locally advanced or metastatic: IV: 840 mg on days 1 and 15 every 4 weeks (in combination with paclitaxel [protein bound]) until disease progression or unacceptable toxicity; paclitaxel (protein bound) or atezolizumab may be discontinued for toxicity independently of each other (Schmid 2018). Note: Select patients for atezolizumab therapy based on the programmed death-ligand 1 (PD-L1) expression on tumor-infiltrating immune cells.

Hepatocellular carcinoma, unresectable or metastatic: IV: 1,200 mg once every 3 weeks (in combination with bevacizumab on the same day) until disease progression or unacceptable toxicity; may continue beyond disease progression if clinical benefit demonstrated (Finn 2020). If bevacizumab is discontinued due to unacceptable toxicity, may continue atezolizumab monotherapy at 840 mg once every 2 weeks or 1,200 mg once every 3 weeks or 1,680 mg once every 4 weeks until disease progression or unacceptable toxicity.

Melanoma, unresectable or metastatic (BRAF V600 mutation-positive): IV: 840 mg once every 2 weeks (in combination with cobimetinib and vemurafenib) until disease progression or unacceptable toxicity; prior to initiating atezolizumab, patients should receive a 28-day treatment cycle of cobimetinib and vemurafenib (Gutzmer 2020). Refer to protocol for further information.

Non-small cell lung cancer (NSCLC), metastatic: IV:

First-line treatment NSCLC (single agent): 840 mg once every 2 weeks or 1,200 mg once every 3 weeks (Jassem 2020) or 1,680 mg once every 4 weeks; continue until disease progression or unacceptable toxicity. Note: Select patients for atezolizumab therapy based on the programmed death-ligand 1 (PD-L1) expression on tumor cells or on tumor-infiltrating immune cells.

First-line treatment, non-squamous NSCLC:

1,200 mg on day 1 every 3 weeks (in combination with bevacizumab, paclitaxel, and carboplatin) for 4 to 6 cycles, followed by atezolizumab 1,200 mg on day 1 (followed by bevacizumab) every 3 weeks until disease progression or unacceptable toxicity (Socinski 2018); if bevacizumab is discontinued after the 4 to 6 cycles of combination chemotherapy, atezolizumab may be continued as a single agent at 840 mg once every 2 weeks or 1,200 mg once every 3 weeks or 1,680 mg once every 4 weeks until disease progression or unacceptable toxicity.

1,200 mg on day 1 every 3 weeks (in combination with paclitaxel [protein bound] and carboplatin) for 4 to 6 cycles (West 2019); after the 4 to 6 cycles of induction combination chemotherapy, atezolizumab may be continued as a single agent at 840 mg once every 2 weeks or 1,200 mg once every 3 weeks or 1,680 mg once every 4 weeks until disease progression or unacceptable toxicity.

Previously-treated NSCLC: 840 mg once every 2 weeks or 1,200 mg once every 3 weeks (Fehrenbacher 2016; Rittmeyer 2017) or 1,680 mg once every 4 weeks; continue until disease progression or unacceptable toxicity.

Small cell lung cancer (extensive stage), first-line treatment: IV: Induction: 1,200 mg on day 1 every 3 weeks in combination with carboplatin and etoposide for 4 cycles (Horn 2018), followed by maintenance therapy of single-agent atezolizumab at 840 mg once every 2 weeks or 1,200 mg once every 3 weeks (Horn 2018) or 1,680 mg once every 4 weeks; continue until disease progression or unacceptable toxicity.

Urothelial carcinoma, locally advanced or metastatic: IV: 840 mg once every 2 weeks or 1,200 mg once every 3 weeks (Balar 2017; Rosenberg 2016) or 1,680 mg once every 4 weeks; continue until disease progression or unacceptable toxicity. Note: Select previously untreated, cisplatin-ineligible patients for atezolizumab therapy based on the PD-L1 expression on tumor-infiltrating immune cells.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Dosage reductions are not recommended for toxicities. Treatment is withheld or permanently discontinued. If therapy is withheld, depending on the toxicity grade, may resume if toxicity recovers to grade 0 or 1. Permanently discontinue for recurrent grade 3 or 4 toxicity. Concomitant chemotherapy may require therapy interruption, dosage reduction, or discontinuation based on toxicity severity.

Cardiovascular toxicity: Myocarditis, pericarditis, arrhythmias, impaired ventricular function with HF, and vasculitis (American Society of Clinical Oncology [ASCO] guidelines for the Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy [Brahmer 2018]): Withhold therapy for all grades and obtain cardiology consultation for work-up and intervention (due to potential for cardiac compromise). For grade 2 or higher myocarditis, consider high-dose corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent), management per cardiology consultation, and permanent discontinuation. The appropriateness of resuming immune checkpoint inhibitor therapy following resolution of myocarditis is unknown.

Endocrinopathies:

Adrenal insufficiency, ≥ grade 2: Withhold treatment. Administer high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper and administer hormone replacement as clinically indicated. May resume atezolizumab when ≤ grade 1 and clinically stable on hormone replacement therapy.

Diabetes mellitus type 1/hyperglycemia, ≥ grade 2: Withhold treatment. May require insulin treatment. May resume atezolizumab when ≤ grade 1 and clinically stable.

Hyperthyroidism, ≥ grade 2: Withhold treatment. May require additional treatment for symptomatic hyperthyroidism. May resume atezolizumab when ≤ grade 1 and clinically stable.

Hypophysitis, ≥ grade 2: Withhold treatment. Administer high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper and administer hormone replacement as clinically indicated. May resume atezolizumab when ≤ grade 1 and clinically stable on hormone replacement therapy.

Hypothyroidism: Continue atezolizumab and initiate hormone replacement therapy.

Gastrointestinal toxicity:

Diarrhea or colitis, grade 2 or 3: Withhold treatment. If symptoms persist for >5 days or recur, administer high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper. May resume when ≤ grade 1 and prednisone dose is ≤10 mg/day (or equivalent).

Diarrhea or colitis, grade 4: Discontinue permanently. Administer high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper.

Infection, ≥ grade 3: Withhold treatment until ≤ grade 1 or resolved.

Infusion-related reactions:

Grade 1 or 2: Interrupt or slow the infusion rate; consider premedication with subsequent doses.

Grade 3 or 4: Permanently discontinue.

Myositis: ASCO guidelines for the Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy (ASCO [Brahmer 2018]):

Grade 1: Continue treatment. May consider acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) for analgesia (if no contraindications). If creatine kinase (CK) is elevated and patient has muscle weakness, consider oral corticosteroids and manage as per grade 2 toxicity.

Grade 2: Temporarily withhold treatment. Administer NSAIDs as needed. Refer to rheumatologist or neurologist for work-up. If CK is elevated ≥3 times, initiate corticosteroids (prednisone at 0.5 to 1 mg/kg/day or equivalent). May resume atezolizumab upon symptom control, if CK is normal, and if prednisone dose is <10 mg/day. If myositis worsens, manage per grade 3. Most patients with grade 2 symptoms and objective findings (elevated enzymes, abnormal electromyography, abnormal muscle MRI or biopsy) may require permanent discontinuation.

Grade 3 or 4: Withhold treatment until symptoms resolve to ≤ grade 1 while off immune suppression (permanently discontinue if there is any evidence of myocardial involvement). Initiate high-dose corticosteroids (prednisone 1 mg/kg/day or equivalent); if severely compromised with cardiac, respiratory, and/or dysphagia symptoms or weakness severely limiting mobility, consider IV methylprednisolone 1 to 2 mg/kg or higher-dose bolus. Refer to rheumatologist or neurologist for work-up. Consider hospitalization for severe weakness. Consider plasmapheresis and IV immunoglobulin therapy. If symptoms and CK levels do not improve or worsen after 4 to 6 weeks, consider other immunosuppressant therapy (eg, methotrexate, azathioprine, mycophenolate mofetil).

Ophthalmic disorders: Uveitis in combination with other immune-mediated adverse reactions may require systemic corticosteroids to reduce the risk of permanent vision loss.

Pulmonary toxicities:

Pneumonitis, grade 2: Withhold treatment. Administer high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper. May resume when ≤ grade 1 and prednisone dose is ≤10 mg/day (or equivalent).

Pneumonitis, grade 3 or 4: Discontinue permanently. Administer high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper.

Other toxicities:

Grade 2 (immune-mediated): Exclude other causes and initiate corticosteroids as clinically indicated.

Grade 3 (immune-mediated; involving a major organ): Withhold treatment. Administer high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper. May resume when ≤ grade 1 and prednisone dose is ≤10 mg/day (or equivalent).

Grade 4 (immune-mediated; involving a major organ): Discontinue permanently. Administer high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent) followed by a corticosteroid taper.

Persistent/resistant/recurrent toxicities:

Persistent grade 2 or 3 toxicity (excluding endocrinopathies) that does not recover to ≤ grade 1 within 12 weeks after last atezolizumab dose: Discontinue permanently.

Inability to taper corticosteroid to prednisone ≤10 mg/day (or equivalent) within 12 weeks after last atezolizumab dose: Discontinue permanently.

Recurrent grade 3 or 4 (severe or life-threatening) toxicity: Discontinue permanently.

Reconstitution

Withdraw dose from vial and dilute with NS to a final concentration between 3.2 to 16.8 mg/mL; infusion bag should be made of PVC, polyethylene (PE), or polyolefin (PO). Dilute only with NS. Mix by gently inverting; do not shake.

Administration

IV: Infuse the initial dose over 60 minutes, if tolerated, may infuse subsequent doses over 30 minutes. May be infused with or without a 0.2- to 0.22-micron sterile, non-pyrogenic, low-protein binding in-line filter. Do not administer as an IV push or bolus. Do not administer other medications at the same time through the same IV line. Monitor for infusion reactions.

When administering in combination with other chemotherapy agents and/or bevacizumab on the same day, administer atezolizumab prior to chemotherapy and/or bevacizumab.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not shake. Store in original carton to protect from light. Solutions diluted in NS for infusion should be used immediately after preparation; if not used immediately, may be stored for up to 6 hours (including administration time) at room temperature or 24 hours refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze or shake.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (urothelial carcinoma: 17% to 18%)

Dermatologic: Pruritus (urothelial carcinoma: 13% to 18%), skin rash (12% to 17%)

Endocrine & metabolic: Hypoalbuminemia (NSCLC: 48%; urothelial carcinoma, grades 3/4: 1%), hypomagnesemia (NSCLC: 26%), hyponatremia (NSCLC: 42%; urothelial carcinoma, grades 3/4: 10% to 15%), hypophosphatemia (NSCLC: 27%; urothelial carcinoma, grades 3/4: 4%)

Gastrointestinal: Abdominal pain (urothelial carcinoma: 15% to 17%), colitis (≤24%; includes immune-mediated), constipation (15% to 21%), decreased appetite (23% to 26%), diarrhea (≤24%), nausea (18% to 25%), vomiting (urothelial carcinoma: 16% to 17%)

Genitourinary: Hematuria (urothelial carcinoma: 14%), urinary tract infection (urothelial carcinoma: 17% to 22%)

Hematologic & oncologic: Anemia (NSCLC: 67%; NSCLC and urothelial carcinoma, grades 3/4: 3% to 8%), lymphocytopenia (NSCLC: 49%; NSCLC and urothelial carcinoma, grades 3/4: 9% to 14%)

Hepatic: Increased serum alanine aminotransferase (NSCLC: 27%; urothelial carcinoma, grades 3/4: 2% to 4%), increased serum alkaline phosphatase (NSCLC: 39%; urothelial carcinoma, grades 3/4: 4% to 7%), increased serum aspartate aminotransferase (NSCLC: 31%; urothelial carcinoma, grades 3/4: 2% to 4%)

Immunologic: Antibody development (NSCLC: 30%; urothelial carcinoma: 42%)

Infection: Infection (42%)

Nervous system: Fatigue (≤52%), pain (NSCLC: ≤20%)

Neuromuscular & skeletal: Arthralgia (12% to 14%), asthenia (≤52%), back pain (≤18%), myalgia (NSCLC: ≤20%), neck pain (urothelial carcinoma: ≤18%)

Renal: Increased serum creatinine (NSCLC: 23%; urothelial carcinoma, grades 3/4: 3% to 5%)

Respiratory: Cough (14% to 26%), dyspnea (12% to 22%)

Miscellaneous: Fever (14% to 21%)

1% to 10%:

Endocrine & metabolic: Hyperglycemia (urothelial carcinoma; grades 3/4: 5% to 10%), hyperkalemia (urothelial carcinoma, grades 3/4: 3%), hypermagnesemia (urothelial carcinoma, grades 3/4: 3%), hyperthyroidism (2%; may be immune-mediated), hypothyroidism (5%; may be immune-mediated)

Hepatic: Hepatitis (9%; includes immune-mediated), hyperbilirubinemia (urothelial carcinoma, grades 3/4: 3%)

Respiratory: Pneumonia (NSCLC, grades 3/4: 4%; also occurred with urothelial carcinoma), pneumonitis (3%; includes immune-mediated)

Miscellaneous: Infusion related reaction (1%)

<1%:

Cardiovascular: Myocarditis, vasculitis

Dermatologic: Bullous dermatitis, erythema multiforme, pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis

Endocrine & metabolic: Adrenocortical insufficiency, hypophysitis, pituitary insufficiency, thyroiditis, type 1 diabetes mellitus (including diabetic ketoacidosis)

Gastrointestinal: Increased serum amylase, increased serum lipase, pancreatitis

Genitourinary: Nephrotic syndrome

Hematologic & oncologic: Autoimmune hemolytic anemia, immune thrombocytopenia, lymphadenitis (histiocytic necrotizing)

Infection: Systemic inflammatory response syndrome

Nervous system: Aseptic meningitis, demyelinating disease, encephalitis, facial paresis, Guillain-Barre syndrome, meningoencephalitis, myasthenia, myasthenia gravis, neuropathy (autoimmune), paresis (abducens nerve)

Neuromuscular & skeletal: Myositis, polymyalgia rheumatica, rhabdomyolysis

Ophthalmic: Iritis, uveitis, Vogt-Koyanagi-Harada syndrome

Renal: Nephritis

Frequency not defined:

Cardiovascular: Pulmonary embolism (NSCLC), venous thromboembolism (urothelial carcinoma)

Endocrine & metabolic: Dehydration (urothelial carcinoma)

Gastrointestinal: Intestinal obstruction (urothelial carcinoma)

Genitourinary: Urinary tract obstruction (urothelial carcinoma)

Hepatic: Abnormal hepatic function tests (NSCLC)

Hypersensitivity: Hypersensitivity reaction (urothelial carcinoma)

Infection: Sepsis

Nervous system: Confusion (urothelial carcinoma)

Renal: Acute renal failure

Respiratory: Pleural effusion (NSCLC), respiratory tract infection

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal insufficiency: Adrenal insufficiency has been reported with atezolizumab (as a single agent and in combination with other anticancer agents), including grade 3 events. The median time to onset was 5.7 months (range: 3 days to 19 months), and resolved in approximately one-quarter of patients. Withhold atezolizumab for grade 2 or higher adrenal insufficiency and administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) followed by a taper and administer hormone replacement as clinically indicated.

• Cardiovascular toxicity: Myocarditis has been reported with atezolizumab (case reports); may be related to the mechanism of action and/or may be immune-mediated. May require treatment interruption, discontinuation, systemic corticosteroids, and/or other immunosuppressive therapy (ASCO [Brahmer 2018]; Perez 2017). Monitor for signs and symptoms of myocarditis.

• Diabetes mellitus: Type 1 diabetes mellitus has been observed with atezolizumab (as a single agent and in combination with other anticancer agents). For type 1 diabetes, initiate insulin treatment as clinically indicated. Monitor for hyperglycemia and other signs/symptoms of diabetes; withhold therapy for grade 2 or higher hyperglycemia.

• Gastrointestinal toxicity: Immune-mediated colitis or diarrhea (defined as requiring systemic corticosteroids) has occurred in patients receiving atezolizumab (as a single agent and in combination with other anticancer agents), some events included grade 3 and grade 4 events. The median time to onset was 1.5 months (range: 1 day to 41 months). Monitor for signs/symptoms of colitis and diarrhea. Withhold treatment for grade 2 or 3 diarrhea or colitis. For grade 2 or higher diarrhea or colitis, if symptoms persist for >5 days or recur, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone equivalent). Discontinue permanently for grade 4 diarrhea or colitis. When required, high-dose systemic corticosteroids were administered for a median duration of 3 to 4 days (range: 1 to 170 days) and then tapered. Diarrhea and colitis resolved in most patients receiving atezolizumab as a single agent.

• Hepatotoxicity: Immune-mediated hepatitis (defined as requiring systemic corticosteroids) and liver test abnormalities, including grades 3 and 4 and fatal cases, have occurred with atezolizumab (as a single agent and in combination with other anticancer agents). The median time to hepatitis onset was 1.4 months (range: 1 day to 25.8 months) and the median duration of hepatitis was 24 days (range: 1 day to 13 months). Monitor for signs/symptoms of hepatitis (during and after treatment) including monitoring liver function tests (AST, ALT, and bilirubin). Administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) followed by a taper for grade 2 or higher transaminase and/or bilirubin elevations. For grade 2 toxicity, withhold treatment until grade 1 or resolved or corticosteroid dose is ≤10 mg/day prednisone (or equivalent); permanently discontinue for grade 3 or 4 immune-mediated hepatitis. When required, high-dose systemic corticosteroids were administered for a median duration of 3 to 6 days (range: 1 to 144 days) and then tapered. Hepatitis resolved in over two-thirds of patients receiving atezolizumab as a single agent.

• Hypophysitis: Hypophysitis has occurred (rarely) in patients receiving atezolizumab (as a single agent and in combination with other anticancer agents). Monitor for signs/symptoms of hypophysitis. Withhold treatment for grade 2 or higher hypophysitis and administer systemic corticosteroid (1 to 2 mg/kg/day prednisone or equivalent) followed by a taper and administer hormone replacement therapy as clinically indicated.

• Infection: Infections have commonly occurred in patients receiving atezolizumab (as a single agent and in combination with other anticancer agents). Grade 3 and higher infections have occurred (including fatal cases), with urinary tract infection and pneumonia being the most common causes of grade 3 or higher infection in patients with urothelial carcinoma and non-small cell lung cancer (NSCLC), respectively. Upper respiratory infection was the most common infection observed in patients with advanced melanoma. Monitor for signs/symptoms of infection. Withhold treatment for grade 3 or higher infections; may resume once clinically stable.

• Infusion-related reactions: Severe or life-threatening infusion reactions have been reported with atezolizumab. The frequency and severity of infusion reactions was similar whether atezolizumab was administered as a single agent or in combination with other anticancer agents, and was similar across the various approved dose ranges (840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks). Monitor for signs/symptoms of infusion reactions. Interrupt or slow the infusion rate in patients with grade 1 or 2 infusion reactions; consider premedication with subsequent doses. Permanently discontinue for grade 3 or 4 infusion reactions.

• Ocular toxicity: Uveitis and iritis have been reported. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving other medications in this drug class and may require systemic corticosteroids to reduce the risk of permanent vision loss.

• Pulmonary toxicity: Immune-mediated pneumonitis and interstitial lung disease (defined as requiring systemic corticosteroids), including grades 3 and 4 and fatal cases, have been reported in patients receiving atezolizumab (as a single agent and in combination with other anticancer agents). The median time to onset was 3.6 months (range: 3 days to 20.5 months) and the median duration was 1.4 months (range: 1 day to 15.1 months). Monitor for signs (with radiographic imaging) and symptoms of pneumonitis. Administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) followed by a taper for grade 2 or higher pneumonitis. For grade 2 toxicity, withhold treatment until grade 1 or resolved or corticosteroid dose is ≤10 mg/day prednisone (or equivalent); permanently discontinue for grade 3 or 4 pneumonitis. Pneumonitis resolved in two-thirds of patients. When required, high-dose systemic corticosteroids were administered for a median duration of 4 to 5 days (range: 1 to 98 days) and then tapered.

• Thyroid disorders: Hypothyroidism, hyperthyroidism, and acute thyroiditis (rare) have occurred with atezolizumab (as a single agent and in combination with other anticancer agents). Monitor thyroid function prior to and periodically during treatment. For hypothyroidism, continue atezolizumab treatment and initiate thyroid replacement therapy as needed. For grade 2 or higher hyperthyroidism, withhold atezolizumab and (if clinically indicated) initiate antithyroid medications.

• Other immune-mediated toxicities: Other immune-mediated adverse events have occurred (as a single agent and in combination with other anticancer agents), including bullous dermatitis, pemphigoid, erythema multiforme, Stevens Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), pancreatitis (including elevations in serum amylase and lipase), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis, autoimmune hemolytic anemia, immune thrombocytopenia (formerly known as immune thrombocytopenic purpura), myositis, rhabdomyolysis, demyelination, immune-related meningoencephalitis, myasthenia syndrome/myasthenia gravis, Guillain-Barre syndrome, aseptic meningitis, encephalitis, facial and abducens nerve paresis, polymyalgia rheumatic, autoimmune neuropathy, nephrotic syndrome, nephritis, and vasculitis. Immune-mediated reactions may involve any organ system; while they usually develop during atezolizumab treatment, immune-mediated reactions may also occur after therapy discontinuation. For suspected grade 2 immune-mediated toxicities, exclude other causes and initiate systemic corticosteroids as clinically indicated. Administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) followed by a taper for grade 3 or 4 adverse reactions. For grade 3 toxicity, withhold treatment until grade 1 or resolved or corticosteroid dose is ≤10 mg/day prednisone (or equivalent); permanently discontinue for grade 4 toxicity.

Other warnings/precautions:

• Appropriate use: For locally advanced or metastatic urothelial cancer (previously untreated) or locally advanced or metastatic triple-negative breast cancer, select patients for atezolizumab therapy based on the programmed death-ligand 1 (PD-L1) expression on tumor-infiltrating immune cells. For first-line treatment of metastatic NSCLC (as a single agent), select patients for atezolizumab therapy based on the PD-L1 expression on tumor cells or on tumor-infiltrating immune cells. For unresectable or metastatic melanoma, select patients for atezolizumab therapy based on the presence of a BRAF V600 mutation. Information on approved tests is available at http://www.fda.gov/companiondiagnostics.

Monitoring Parameters

PD-L1 expression status (in patients with cisplatin-ineligible locally advanced or metastatic urothelial cancer, locally advanced or metastatic triple-negative breast cancer, or metastatic non-small cell lung cancer [first-line, single-agent therapy]); BRAF V600 mutation status (in patients with unresectable or metastatic melanoma). Monitor liver function tests (AST, ALT, and bilirubin; at baseline and periodically during treatment), thyroid function (prior to and periodically during treatment), serum glucose. Pregnancy test (prior to treatment initiation in females of reproductive potential). Monitor for signs/symptoms of colitis, diarrhea, endocrinopathies, hepatitis, hypophysitis, infection, infusion reactions, cardiovascular toxicity (myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure, and vasculitis), myositis, pneumonitis, and ocular toxicity.

Reproductive Considerations

Verify pregnancy status prior to treatment initiation in females of reproductive potential.

Females of reproductive potential should use effective contraception during therapy and for at least 5 months after the last atezolizumab dose.

Pregnancy Considerations

Based on the mechanism of action, atezolizumab is expected to cause fetal harm if used during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling tired or weak

• Lack of appetite

• Nausea

• Vomiting

• Constipation

• Bone pain

• Neck pain

• Muscle pain

• Joint pain

• Headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infusion reaction like back pain, neck pain, chills, tremors, dizziness, passing out, fever, flushing, itching, rash, shortness of breath, swelling of the face, or wheezing

• Bowel problems like black, tarry, or bloody stools; fever; mucus in stools; vomiting; vomiting blood; severe abdominal pain; constipation; or diarrhea

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain

• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Thyroid, pituitary, or adrenal gland problems like mood changes, behavioral changes, weight changes, constipation, deeper voice, dizziness, passing out, cold sensation, severe fatigue, hair loss, persistent headache, or decreased sex drive

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting

• Nervous system problems like mood changes, behavioral changes, confusion, fever, numbness or tingling in hands or feet, neck rigidity, sensitivity to light, or severe muscle weakness

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.

• High blood pressure like severe headache or dizziness, passing out, or vision changes

• Infection

• Chest pain

• Coughing up blood

• Confusion

• Blurred vision

• Severe back pain

• Severe abdominal pain

• Fast heartbeat

• Abnormal heartbeat

• Shortness of breath

• Swelling of arms or legs

• Bruising

• Bleeding

• Vision changes

• Eye pain

• Severe eye irritation

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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