Atezolizumab

Grades 1 to 3 adrenal insufficiency have been reported. For symptomatic adrenal insufficiency, withhold atezolizumab treatment and administer IV methylprednisolone 1 to 2 mg/kg/day and convert to oral prednisone 1 to 2 mg/kg/day or equivalent upon improvement in symptoms. When symptoms improve to grade 1 or lower, begin to taper steroids over at least 1 month. Resume atezolizumab treatment if symptoms improves to grade 0 or 1 within 12 weeks and corticosteroids have been reduced to oral prednisone ≤10 mg/day and patient is stable on adrenal replacement therapy (if needed).

Myocarditis has been reported with atezolizumab (case reports); may be related to the mechanism of action and/or may be immune-mediated. Discontinue atezolizumab for any grade myocarditis; may require systemic corticosteroids and/or other immunosuppressive therapy (Perez 2017).

New-onset diabetes with ketoacidosis has been observed with atezolizumab. For type 1 diabetes, initiate insulin treatment. For grade 3 or higher hyperglycemia (fasting blood glucose >250 to 500 mg/dL), withhold atezolizumab; resume when metabolic control is achieved on insulin therapy.

Immune-mediated colitis or diarrhea (defined as requiring corticosteroids and with no clear alternative etiology) has occurred in nearly one-fifth of patients receiving atezolizumab, some events included grade 3 and 4 diarrhea. The median onset for some patients was 21 days to 1.7 months (range: 12 days to 3.4 months). Monitor for signs/symptoms of colitis and diarrhea. Withhold treatment for grade 2 or 3 diarrhea or colitis. For grade 2 diarrhea or colitis, if symptoms persist for >5 days or recur, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone equivalent). For grade 3 diarrhea or colitis, administer IV methylprednisolone 1 to 2 mg/kg/day and convert to oral corticosteroids upon improvement in symptoms. If grade 2 and 3 symptoms improve to grade 0 or 1, taper corticosteroids over at least 1 month. Resume atezolizumab treatment if improves to grade 0 or 1 within 12 weeks and corticosteroids have been reduced to oral prednisone ≤10 mg/day. Discontinue permanently for grade 4 diarrhea or colitis. Pancreatitis, increases in amylase and lipase levels, and symptomatic pancreatitis (without other etiology) have occurred with atezolizumab. Monitor for signs/symptoms of acute pancreatitis. Discontinue permanently for grade 4 or any grade recurrent pancreatitis. Withhold treatment for grade 3 or higher serum amylase or lipase increases, or for grade 2 or 3 pancreatitis. Administer IV methylprednisolone 1 to 2 mg/kg/day and convert to oral corticosteroids (prednisone

Immune-mediated hepatitis (defined as requiring corticosteroids and with no clear alternative etiology), including fatal cases, has occurred with atezolizumab. Liver test abnormalities have been reported, including grade 3 and 4 events. The median time to onset was ~1 month (range: 0.4 to 7.7 months). Monitor for signs/symptoms of hepatitis; monitor liver function tests (AST, ALT, and bilirubin) prior to treatment initiation and periodically throughout therapy. Administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) followed by a taper for grade 2 or higher transaminase elevations (with or without elevated bilirubin). Withhold treatment until resolution for grade 2 and permanently discontinue for grade 3 or 4 immune-mediated hepatitis. Patients with treatment interruption for immune-mediated hepatitis did not have recurrence upon resuming treatment.

Hypophysitis has occurred in patients receiving atezolizumab (rare). Monitor for signs/symptoms of hypophysitis. Administer corticosteroids and hormone replacement as indicated. Withhold treatment for grade 2 or 3 hypophysitis; discontinue permanently for grade 4 hypophysitis.

Infections occurred in over 1/3 of patients receiving atezolizumab. Grade 3 and 4 infections have occurred, 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, respectively. There have been case reports of fatal infections. Serious infections, including sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage have been reported. Monitor for signs/symptoms of infection. Manage suspected and confirmed bacterial infections with antibiotics. Withhold treatment for grade 3 or higher infections.

Severe infusion reactions have been reported in clinical trials. Interrupt or slow the infusion rate in patients with mild to moderate infusion reactions. Permanently discontinue for grade 3 or 4 infusion reactions.

Immune-mediated pneumonitis and interstitial lung disease (defined as requiring corticosteroids and with no clear alternative etiology), including fatal cases, have been reported in patients receiving atezolizumab. The median time to onset was 2.6 to 3.3 months (range: 3 days to 18.7 months) and the median duration was 15 days to 1.4 months (range: up to 12.6 months or longer). 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. Withhold treatment until resolution for grade 2 pneumonitis; permanently discontinue for grade 3 or 4 pneumonitis.

Hypothyroidism occurred in patients who received atezolizumab (including grades 1, 2, and 3 events), with a median time to first onset of 4.8 to 5.4 months (range: 15 days to 31 months). Hyperthyroidism was also reported, including grades 1 and 2 events, with a median onset of 3.2 to 4.9 months (range: 21 days to 31 months). Monitor thyroid function prior to and periodically during treatment. Patients with abnormal thyroid function tests who are asymptomatic can receive atezolizumab treatment. For symptomatic hypothyroidism, withhold atezolizumab treatment and initiate thyroid replacement therapy as needed. Isolated hypothyroidism should be managed with replacement therapy and without corticosteroids. For symptomatic hyperthyroidism, withhold atezolizumab and initiate antithyroid medications as needed. Resume atezolizumab treatment when symptoms of hypo- or hyperthyroidism are controlled and thyroid function is improving.

Other immune-mediated adverse events have occurred, including meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barre syndrome, and ocular inflammatory toxicity. Monitor for clinical signs/symptoms of meningitis and encephalitis; discontinue permanently for any grade meningitis or encephalitis; administer IV corticosteroids (methylprednisolone 1 to 2 mg/kg/day) and convert to oral therapy (prednisone 60 mg/day or equivalent) upon improvement; when symptoms improve to grade 1 or lower, taper corticosteroids over at least 1 month. Monitor for neuropathy (motor and sensory); permanently discontinue for any grade myasthenic syndrome/myasthenia gravis or Guillain-Barre syndrome and begin appropriate medical management; consider systemic corticosteroids (prednisone 1 to 2 mg/kg/day). Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.