Managing select TECENTRIQ immune-related adverse events Managing select TECENTRIQ immune-related adverse events

RECOMMENDATIONS FROM THE TECENTRIQ® PRESCRIBING INFORMATION 1

  • This information should not be a substitute for the treating physician's professional medical judgment and should be individualized for the patient 
  • Side effects may be reported to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch or to Genentech at 1-888-835-2555

For more information, please refer to the TECENTRIQ Prescribing Information.

MONITOR

Patient symptoms may include

  • New or worsening cough
  • Shortness of breath
  • Chest pain

MANAGE AND FOLLOW UP

Grade 2
pneumonitis

  • Withhold TECENTRIQ
    • Administer steroids at a dose of 1 to 2 mg/kg/day prednisone equivalents
    • Taper corticosteroids

If adverse event recovers to grade 0 to 1

  • Resume TECENTRIQ

Grade 3 or 4
pneumonitis

  • Permanently discontinue TECENTRIQ
    • Administer steroids at a dose of 1 to 2 mg/kg/day prednisone equivalents
    • Taper corticosteroids
  • Immune-mediated pneumonitis* or interstitial lung disease, including 2 fatal cases, occurred with TECENTRIQ treatment
  • Across clinical trials, 2.6% of patients developed pneumonitis
  • In 523 patients with urothelial carcinoma who received TECENTRIQ, pneumonitis occurred in 6 (1.1%) patients

*Immune-mediated adverse events are defined as requiring the use of corticosteroids and having no clear alternate etiology.

MONITOR

Monitor your patients for signs or symptoms of hepatitis

  • Monitor AST, ALT, and bilirubin prior to and periodically during treatment with TECENTRIQ

Patient symptoms may include

  • Yellowing of skin or the whites of the eyes
  • Severe nausea or vomiting
  • Pain on the right side of the abdomen
  • Drowsiness
  • Dark urine (tea colored)
  • Bleeding or bruising more easily than normal
  • Feeling less hungry than usual

ALT=alanine aminotransferase; AST=asparate aminotransferase; ULN=upper limit of normal.
 

MANAGE AND FOLLOW UP

Grade 2
immune-mediated hepatitis or AST or ALT >3 and ≤5 times ULN, or total bilirubin >1.5 and ≤3 times ULN

  • Withhold TECENTRIQ
    • Administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents*
    • Taper corticosteroids

If adverse event recovers to grade 0 to 1

  • Resume TECENTRIQ

Grade 3 or 4
immune-mediated hepatitis or AST or ALT >5 times ULN, or total bilirubin >3 times ULN

  • Permanently discontinue TECENTRIQ
    • Administer corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents*
    • Taper corticosteroids

*With or without concomitant elevation in total bilirubin.

  • Immune-mediated hepatitis, including a fatal case, and liver test abnormalities have occurred with TECENTRIQ treatment
  • Across clinical trials, grade 3 or 4 elevation occurred in ALT (2.5% of patients), AST (2.3%), and total bilirubin (1.6%). In urothelial carcinoma, immune-mediated hepatitis occurred in 1.3% of patients

Immune-mediated adverse events are defined as requiring the use of corticosteroids and having no clear alternate etiology.

MONITOR

Patient symptoms may include

  • Diarrhea or more bowel movements than usual
  • Blood in stools or dark, tarry, sticky stools
  • Severe abdomen pain or tenderness

IV=intravenous.

MANAGE AND FOLLOW UP

Grade 2
diarrhea or colitis

  • Withhold TECENTRIQ

If symptoms persist for >5 days or recur

  • Administer 1 to 2 mg/kg/day of prednisone or equivalent

When symptoms improve to grade 0 or 1

  • Taper steroids over ≥1 month

If event improves to grade 0 or 1 within 12 weeks
and corticosteroids have been reduced to the equivalent of ≤10 mg/day oral prednisone

  • Resume TECENTRIQ

Grade 3
diarrhea or colitis

  • Withhold TECENTRIQ
    • Treat with IV methylprednisolone 1 to 2 mg/kg/day

Once patient has improved

  • Convert to oral steroids

When symptoms improve to grade 0 or 1

  • Taper steroids over ≥1 month

If event improves to grade 0 or 1 within 12 weeks
and corticosteroids have been reduced to the equivalent of ≤10 mg/day oral prednisone

  • Resume TECENTRIQ

Grade 4
diarrhea or colitis

  • Permanently discontinue TECENTRIQ
  • Immune-mediated colitis or diarrhea,* including a fatal case of diarrhea-associated renal failure, have occurred with TECENTRIQ treatment
  • Across clinical trials, colitis or diarrhea occurred in 19.7% of patients
  • In urothelial carcinoma, immune-mediated colitis or diarrhea* occurred in 0.8% of patients

*Immune-mediated adverse events are defined as requiring the use of corticosteroids and having no clear alternate etiology.

MONITOR

Monitor thyroid function prior to and periodically during treatment with TECENTRIQ


Patient symptoms may include

  • Headaches that will not go away or unusual headaches
  • Extreme tiredness
  • Weight gain or weight loss
  • Dizziness or fainting
  • Feeling more hungry or thirsty than usual
  • Hair loss
  • Changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
  • Feeling cold
  • Constipation
  • Voice gets deeper
  • Urinating more often than usual
  • Nausea or vomiting
  • Abdominal pain

IV=intravenous.

MANAGE AND FOLLOW UP

Grade 2 or 3 hypophysitis

  • Withhold TECENTRIQ
    • Administer corticosteroids and hormone replacement as needed

If adverse event recovers to grade 0 to 1

  • Resume TECENTRIQ

 

Grade 4 hypophysitis

  • Permanently discontinue TECENTRIQ
    • Administer corticosteroids and hormone replacement as needed

Symptomatic hypothyroidism

  • Withhold TECENTRIQ
    • Initiate thyroid hormone replacement, as needed
    • Manage isolated hypothyroidism with replacement therapy and without corticosteroids

When symptoms are controlled
and thyroid function is improved

  • Resume TECENTRIQ

 Symptomatic hyperthyroidism

  • Withhold TECENTRIQ
    • Initiate antithyroid drug, as needed

When symptoms are controlled
and thyroid function is improved

  • Resume TECENTRIQ

Asymptomatic hypothyroidism or hyperthyroidism

Asymptomatic patients with abnormal thyroid function tests can continue receiving TECENTRIQ


Symptomatic adrenal insufficiency

  • Withhold TECENTRIQ
    • Administer methylprednisolone 1 to 2 mg/kg/day IV

Once symptoms improve

  • Follow with oral prednisone 1 to 2 mg/kg/day or equivalent

When symptoms improve to ≤grade 1

  • Taper steroids over ≥1 month

If event improves to ≤grade 1 within 12 weeks
and corticosteroids have been reduced to the equivalent of ≤10 mg/day oral prednisone
and the patient is stable on replacement therapy, if required

  • Resume TECENTRIQ

Type 1 diabetes mellitus

For grade 3 or 4 hyperglycemia (fasting glucose >250-500 mg/dL)

  • Withhold TECENTRIQ
    • Initiate treatment with insulin

When metabolic control is achieved on insulin replacement therapy

  • Resume TECENTRIQ
  • Immune-related thyroid disorders, adrenal insufficiency, hypophysitis, and type 1 diabetes mellitus, including diabetic ketoacidosis, have occurred in patients receiving TECENTRIQ
  • Across clinical trials, hypothyroidism and hyperthyroidism occurred in 3.9% and 1.0% of patients, respectively
  • Across clinical trials, adrenal insufficiency occurred in 0.4% of patients
  • In urothelial carcinoma, hypophysitis occurred in 0.2% of patients
  • New onset diabetes with ketoacidosis occurred in patients. Diabetes mellitus without an alternative etiology occurred in 0.2% of patients with urothelial carcinoma

MONITOR

Patient symptoms may include

  • Severe muscle weakness
  • Numbness or tingling in hands and feet
  • Fever
  • Confusion
  • Changes in mood or behavior
  • Extreme sensitivity to light
  • Neck stiffness
  • Blurry vision, double vision, or other vision problems
  • Eye pain or redness
  • Nausea or vomiting
  • Abdominal pain

IV=intravenous; ULN=upper limit of normal.

MANAGE AND FOLLOW UP

Any grade meningitis or encephalitis

  • Permanently discontinue TECENTRIQ
    • Treat with IV steroids 1 to 2 mg/kg/day methylprednisolone or equivalent

Once patient has improved

  • Convert to oral steroids prednisone 60 mg/day or equivalent

When symptoms improve to ≤grade 1

  • Taper steroids over ≥1 month

Any grade myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome

  • Permanently discontinue TECENTRIQ
    • Institute medical intervention, as appropriate
    • Consider initiation of systemic corticosteroids at a dose of 1 to 2 mg/kg/day prednisone

Grade 2 ocular inflammatory toxicity

  • Withhold TECENTRIQ

If adverse event recovers to grade 0 to 1

  • Resume TECENTRIQ

 

Grade 3 or 4 ocular inflammatory toxicity

  • Permanently discontinue TECENTRIQ

Grade 2 or 3 pancreatitis
or
Grade 3 or 4 serum amylase or lipase levels increased (>2.0 ULN)

  • Withhold TECENTRIQ
    • Treat with 1 to 2 mg/kg/day IV methylprednisolone or equivalent

Once symptoms improve

  • Follow with 1 to 2 mg/kg/day oral prednisone or equivalent

When serum amylase lipase levels improve to ≤grade 1 within 12 weeks
or symptoms of pancreatitis have resolved
and corticosteroids have been reduced to the equivalent of ≤10 mg/day oral prednisone

  • Resume TECENTRIQ

 

Grade 4 or any grade of recurrent pancreatitis

  • Permanently discontinue TECENTRIQ
  • Other immune-related adverse reactions, including meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, ocular inflammatory toxicity, and pancreatitis, including increases in serum amylase and lipase levels, have occurred in ≤1.0% of patients treated with TECENTRIQ
  • Symptomatic pancreatitis without an alternative etiology occurred in 0.1% of patients across clinical trials

MONITOR

Patient symptoms may include

  • Fever
  • Cough
  • Frequent urination
  • Flu-like symptoms
  • Pain when urinating

MANAGE AND FOLLOW UP

Grade 3 or 4
infection
 

  • Withhold TECENTRIQ
    • Treat with antibiotics for suspected or confirmed bacterial infections

If adverse event recovers to grade 0 to 1

  • Resume TECENTRIQ
  • Severe infections, including sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage occurred in patients receiving TECENTRIQ 
  • Across clinical trials, infections occurred in 38.4% of patients
  • In urothelial carcinoma, infection occurred in 37.7% of patients. Grade 3 or 4 infection occurred in 11.5% of patients, while 3 patients died due to infections

MONITOR

Patient symptoms may include

  • Chills or shaking
  • Itching or rash
  • Flushing
  • Shortness of breath or wheezing
  • Swelling of the face or lips
  • Dizziness
  • Fever
  • Feeling like passing out
  • Back or neck pain

MANAGE AND FOLLOW UP

Grade 2
infusion-related reactions

  • Withhold TECENTRIQ
    • Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions

If adverse event recovers to grade 0 to 1

  • Resume TECENTRIQ

Grade 3 or 4
infusion-related reactions

  • Permanently discontinue TECENTRIQ
  • Severe infusion reactions have occurred in patients in clinical trials of TECENTRIQ. Infusion-related reactions occurred in 1.7% in urothelial carcinoma

INDICATION

TECENTRIQ (atezolizumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:

  • Are not eligible for cisplatin-containing chemotherapy, or
  • Have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Serious Adverse Reactions
Please refer to the full Prescribing Information for important dose management information specific to adverse reactions.

Immune-Related Pneumonitis

  • Immune-mediated pneumonitis or interstitial lung disease, including 2 fatal cases, occurred with TECENTRIQ treatment
  • Across clinical trials, 2.6% of patients developed pneumonitis
  • Monitor patients for signs with radiographic imaging and symptoms of pneumonitis. Administer steroids for ≥Grade 2 pneumonitis. Withhold TECENTRIQ until resolution of Grade 2 pneumonitis. Permanently discontinue for Grade 3 or 4 pneumonitis

Immune-Related Hepatitis

  • Immune-mediated hepatitis, including a fatal case, and liver test abnormalities have occurred with TECENTRIQ treatment
  • Across clinical trials, Grade 3 or 4 elevation occurred in ALT (2.5%), AST (2.3%), and total bilirubin (1.6%). In patients with urothelial carcinoma (UC), immune-mediated hepatitis occurred in 1.3% of patients
  • Monitor patients for signs and symptoms of hepatitis. Monitor AST, ALT, and bilirubin prior to and periodically during treatment
  • Administer corticosteroids for ≥Grade 2 transaminase elevations, with or without concomitant elevation in total bilirubin. Withhold TECENTRIQ for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis

Immune-Related Colitis

  • Immune-mediated colitis or diarrhea, including a fatal case of diarrhea-associated renal failure, have occurred with TECENTRIQ treatment
  • Across clinical trials, colitis or diarrhea occurred in 19.7% of patients. In UC, immune-mediated colitis or diarrhea occurred in 0.8% of patients
  • Monitor patients for signs and symptoms of diarrhea or colitis. Withhold TECENTRIQ for Grade 2 or Grade 3 diarrhea or colitis. Permanently discontinue for Grade 4 diarrhea or colitis

Immune-Related Endocrinopathies

  • Immune-related thyroid disorders, adrenal insufficiency, hypophysitis, and type 1 diabetes mellitus, including diabetic ketoacidosis, have occurred in patients receiving TECENTRIQ. Monitor patients for clinical signs and symptoms of endocrinopathies
  • Across clinical trials hypo- and hyperthyroidism occurred in 3.9% and 1.0% of patients, respectively. For symptomatic hypothyroidism, withhold TECENTRIQ and initiate hormone replacement as needed. Manage isolated hypothyroidism with replacement therapy and without corticosteroids. For symptomatic hyperthyroidism, withhold TECENTRIQ and initiate an anti-thyroid drug as needed
  • Across clinical trials, adrenal insufficiency occurred in 0.4% of patients. For symptomatic adrenal insufficiency, withhold TECENTRIQ and administer corticosteroids
  • Hypophysitis occurred in 0.2% of patients with UC. Administer corticosteroids and hormone replacement as clinically indicated. Withhold for Grade 2 or Grade 3, and permanently discontinue for Grade 4 hypophysitis
  • New onset diabetes with ketoacidosis occurred in patients. Diabetes mellitus without an alternative etiology occurred in 0.2% of patients with urothelial carcinoma. Initiate treatment with insulin for type 1 diabetes mellitus. For ≥Grade 3 hyperglycemia (fasting glucose >250-500 mg/dL), withhold TECENTRIQ

Other Immune-Related Adverse Reactions

  • Other immune-related adverse reactions, including meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, ocular inflammatory toxicity, and pancreatitis, including increases in serum amylase and lipase levels, have occurred in ≤1.0% of patients treated with TECENTRIQ
  • Symptomatic pancreatitis without an alternative etiology occurred in 0.1% of patients across clinical trials
  • Monitor patients for clinical signs and symptoms of meningitis or encephalitis, as well as symptoms of motor and sensory neuropathy. Permanently discontinue TECENTRIQ for any grade of meningitis or encephalitis or any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome
  • Monitor patients for signs and symptoms of acute pancreatitis. Withhold TECENTRIQ for ≥Grade 3 serum amylase or lipase levels (>2.0 ULN), or Grade 2 or 3 pancreatitis. Permanently discontinue for Grade 4 or any grade of recurrent pancreatitis

Infection

  • Severe infections, including sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage occurred in patients receiving TECENTRIQ
  • Across clinical trials, infections occurred in 38.4% of patients
  • In urothelial carcinoma, infection occurred in 37.7% of patients. Grade 3 or 4 infection occurred in 11.5% of patients, while 3 patients died due to infections. Urinary tract infections were the most common cause of Grade 3 or higher infection, occurring in 7.1% of patients
  • Monitor patients for signs and symptoms of infection and treat with antibiotics for suspected or confirmed bacterial infections. Withhold TECENTRIQ for ≥Grade 3 infection

Infusion-Related Reactions

  • Severe infusion reactions have occurred in patients in clinical trials of TECENTRIQ. Infusion-related reactions occurred in 1.7% in UC
  • Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions. Permanently discontinue TECENTRIQ in patients with Grade 3 or 4 infusion reactions

Embryo-Fetal Toxicity

  • Based on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman. Advise pregnant women or women planning to become pregnant of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECENTRIQ and for at least 5 months after the last dose of TECENTRIQ

Nursing Mothers

  • Because of the potential for serious adverse reactions in breastfed infants from TECENTRIQ, advise female patients not to breastfeed while taking TECENTRIQ and for at least 5 months after the last dose

Most Common Adverse Reactions

The most common adverse reactions in cisplatin-ineligible UC (rate ≥20%) were fatigue (52%), decreased appetite (24%), diarrhea (24%), and nausea (22%).

The most common adverse reactions (rate ≥20%) in previously treated UC were fatigue (52%), decreased appetite (26%), nausea (25%), urinary tract infection (22%), pyrexia (21%), and constipation (21%).

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety Information.