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

Monitor patients for signs and symptoms of pneumonitis

  • Evaluate patients with suspected pneumonitis with radiographic imaging

Patient symptoms may include

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

MANAGE AND FOLLOW UP

Grade 2
Pneumonitis

  • Withhold TECENTRIQ
    • Administer corticosteroids, prednisone 1 to 2 mg/kg/day or equivalents
    • Taper corticosteroids

When adverse reaction recovers to grade 1 or is resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)

  • Resume TECENTRIQ

Grade 3 or 4
Pneumonitis

  • Permanently discontinue TECENTRIQ
    • Administer corticosteroids, prednisone 1 to 2 mg/kg/day or equivalents
    • Taper corticosteroids

SELECT IMPORTANT SAFETY INFORMATION

  • Immune-mediated pneumonitis* or interstitial lung disease, including fatal cases, have occurred with TECENTRIQ treatment
  • Across clinical trials, 2.5% of patients developed pneumonitis, including Grade 3 (0.6%), Grade 4 (0.1%), and Grade 5 (<0.1%) events

*Immune-mediated adverse reactions are defined as requiring the use of corticosteroids.

MONITOR

Monitor patients for signs or symptoms of hepatitis, during and after discontinuation of TECENTRIQ, including clinical chemistry monitoring


Patient symptoms may include

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

MANAGE AND FOLLOW UP

Immune-mediated hepatitis or AST or ALT >3 and ≤8 times ULN, or total bilirubin >1.5 and ≤3 times ULN

  • Withhold TECENTRIQ
    • Administer corticosteroids, prednisone 1 to 2 mg/kg/day or equivalents
    • Taper corticosteroids

When adverse reaction recovers to grade 1 or is resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)

  • Resume TECENTRIQ

Immune-mediated hepatitis or AST or ALT >8 times ULN, or total bilirubin >3 times ULN

  • Permanently discontinue TECENTRIQ
    • Administer corticosteroids, prednisone 1 to 2 mg/kg/day or equivalents
    • Taper corticosteroids

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

SELECT IMPORTANT SAFETY INFORMATION

  • Liver test abnormalities and immune-mediated hepatitis,* including fatal cases, have occurred with TECENTRIQ treatment
  • Across clinical trials, hepatitis occurred in 9% of patients, including Grade 3 (2.3%), Grade 4 (0.6%), and Grade 5 (<0.1%) events

Immune-mediated adverse reactions are defined as requiring the use of corticosteroids.

MONITOR

Monitor patients for signs and symptoms of colitis or diarrhea


Patient symptoms may include

  • Diarrhea (loose stools) or more bowel movements than usual
  • Blood or mucous in your stools or dark, tarry, sticky stools
  • Severe stomach area (abdomen) pain or tenderness

MANAGE AND FOLLOW UP

Grade 2 or 3
Colitis or diarrhea

  • Withhold TECENTRIQ

If symptoms persist for >5 days or recur

  • Administer corticosteroids, prednisone 1 to 2 mg/kg/day or equivalents
  • Taper corticosteroids

When adverse reaction recovers to grade 1 or is resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)

  • Resume TECENTRIQ

Grade 4
Colitis or diarrhea

  • Permanently discontinue TECENTRIQ

SELECT IMPORTANT SAFETY INFORMATION

  • Immune-mediated colitis or diarrhea* have occurred with TECENTRIQ treatment
  • Across clinical trials, diarrhea or colitis occurred in 20% of patients, including Grade 3 (1.4%) events

*Immune-mediated adverse reactions are defined as requiring the use of corticosteroids.

MONITOR

Monitor thyroid function prior to and periodically during treatment with TECENTRIQ

Additionally, monitor patients for clinical signs and symptoms of

  • Adrenal insufficiency
  • Hyperglycemia or other signs and symptoms of diabetes

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

MANAGE AND FOLLOW UP

For grade 2, 3, or 4 endocrinopathies, withhold TECENTRIQ until grade 1 or resolved and clinically stable on hormone replacement therapies. See below for information on the management of select endocrinopathies


Grade 2, 3, or 4

Hyperthyroidism

  • Withhold TECENTRIQ based on the severity
    • Initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated

When adverse reaction recovers to grade 1 or is resolved and clinically stable on hormone replacement therapy

  • Resume TECENTRIQ

Hypothyroidism

  • Continue TECENTRIQ

Grade 2, 3, or 4

Adrenal Insufficiency

  • Withhold TECENTRIQ based on the severity
    • Initiate prednisone 1 to 2 mg/kg/day or equivalents
    • Follow with a taper and hormone replacement as clinically indicated

When adverse reaction recovers to grade 1 or is resolved and clinically stable on hormone replacement therapy

  • Resume TECENTRIQ

Grade 2, 3, or 4

Type 1 Diabetes Mellitus

  • Withhold TECENTRIQ based on the severity
    • Initiate treatment with insulin as clinically indicated

When adverse reaction recovers to grade 1 or is resolved and clinically stable on hormone therapy

  • Resume TECENTRIQ

Grade 2, 3, or 4

Hypophysitis 

  • Withhold TECENTRIQ based on the severity
    • Initiate prednisone 1 to 2 mg/kg/day or equivalents
    • Follow with a taper and hormone replacement as clinically indicated

 When adverse reaction recovers to grade 1 or is resolved and clinically stable on hormone replacement therapy

  • Resume TECENTRIQ

SELECT IMPORTANT SAFETY INFORMATION

  • TECENTRIQ can cause immune-mediated endocrinopathies,* including thyroid disorders, adrenal insufficiency, and type 1 diabetes mellitus, including diabetic ketoacidosis, and hypophysitis/hypopituitarism
  • Thyroid Disorders
    • Across clinical studies, hypothyroidism occurred in 4.6% of patients and hyperthyroidism occurred in 1.6% of patients
  • Adrenal Insufficiency
    • Across clinical studies, adrenal insufficiency occurred in 0.4% of patients, including Grade 3 (<0.1%) events
  • Type 1 Diabetes Mellitus
    • Across clinical studies, type 1 diabetes mellitus occurred in <0.1% of patients
  • Hypophysitis
    • Across clinical studies, Grade 2 hypophysitis occurred in <0.1% of patients

*Immune-mediated adverse reactions are defined as requiring the use of corticosteroids.

MONITOR

Monitor patients for signs and symptoms of immune-mediated adverse reactions*

Patient symptoms may include

  • Severe muscle weakness
  • Numbness or tingling in hands or feet
  • Confusion
  • Blurry vision, double vision, or other vision problems
  • Changes in mood or behavior
  • Extreme sensitivity to light
  • Neck stiffness
  • Eye pain or redness
  • Skin blisters or peeling
  • Chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles

MANAGE AND FOLLOW UP

Grade 2

Other immune-mediated adverse reactions involving a major organ

For suspected grade 2 immune-mediated adverse reactions, exclude other causes and initiate corticosteroids as clinically indicated


Grade 3

 Other immune-mediated adverse reactions involving a major organ

  •  Withhold TECENTRIQ
    •  Administer corticosteroids, prednisone 1 to 2 mg/kg/day or equivalents
    •  Taper corticosteroids

When adverse reaction recovers to grade 1 or is resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)

  • Resume TECENTRIQ   

Grade 4

 Other immune-mediated adverse reactions involving a major organ

  • Permanently discontinue TECENTRIQ
    • Administer corticosteroids, prednisone 1 to 2 mg/kg/day or equivalents
    • Taper corticosteroids

SELECT IMPORTANT SAFETY INFORMATION

  • TECENTRIQ can cause severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system
  • Across clinical trials, cardiac, dermatologic, gastrointestinal, general, hematological, musculoskeletal, neurological, ophthalmological, renal, and vascular immune-mediated adverse reactions occurred at an incidence of <1% in patients who received TECENTRIQ or were reported for other products in this class of therapy

*Immune-mediated adverse reactions include cardiac, dermatologic, gastrointestinal, general, hematological, musculoskeletal, neurological, ophthalmological, renal, and vascular.
Immune-mediated adverse reactions are defined as requiring the use of corticosteroids.

MONITOR

Monitor patients for signs and symptoms of infection

Patient symptoms may include

  • Fever
  • Cough
  • Flu-like symptoms
  • Pain when urinating, frequent urination, or back pain

MANAGE AND FOLLOW UP

Grade 3 or 4
Infections
 

  • Withhold TECENTRIQ

When adverse reaction recovers to grade 1 or is resolved

  • Resume TECENTRIQ

SELECT IMPORTANT SAFETY INFORMATION

  • TECENTRIQ can cause severe infections including fatal cases
  • Across clinical trials, infections occurred in 42% of patients, including Grade 3 (8.7%), Grade 4 (1.5%), and Grade 5 (1%) events

MONITOR

Monitor patients for signs and symptoms of infusion-related reactions

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 1 or 2
Infusion-related reactions

  • Interrupt or slow the rate of infusion
    • Consider using premedications with subsequent doses

Grade 3 or 4
Infusion-related reactions

  • Permanently discontinue TECENTRIQ

SELECT IMPORTANT SAFETY INFORMATION

  • TECENTRIQ can cause severe or life-threatening infusion-related reactions
  • Across clinical trials, infusion-related reactions occurred in 1.3% of patients, including Grade 3 (0.2%) events

IMPORTANT SAFETY INFORMATION AND INDICATION

Indication

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

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

Immune-Mediated Pneumonitis

  • Immune-mediated pneumonitis or interstitial lung disease, including fatal cases, have occurred with TECENTRIQ treatment
  • Across clinical trials, 2.5% of patients developed pneumonitis, including Grade 3 (0.6%), Grade 4 (0.1%), and Grade 5 (<0.1%) events
  • Monitor patients for signs and symptoms of pneumonitis. Evaluate patients with suspected pneumonitis with radiographic imaging. Administer corticosteroids followed by a taper. Withhold TECENTRIQ for Grade 2 and permanently discontinue for Grade 3 or 4 pneumonitis

Immune-Mediated Hepatitis

  • Liver test abnormalities and immune-mediated hepatitis, including fatal cases, have occurred with TECENTRIQ treatment
  • Across clinical trials, hepatitis occurred in 9% of patients, including Grade 3 (2.3%), Grade 4 (0.6%), and Grade 5 (<0.1%) events
  • Monitor patients for signs and symptoms of hepatitis, during and after discontinuation of TECENTRIQ, including clinical chemistry monitoring. Administer corticosteroids followed by a taper for immune-mediated hepatitis. Withhold TECENTRIQ for AST or ALT elevations more than 3 and up to 8 times the upper limit of normal or total bilirubin more than 1.5 and up to 3 times the upper limit of normal. Permanently discontinue TECENTRIQ for AST or ALT elevations more than 8 times the upper limit of normal or total bilirubin more than 3 times the upper limit of normal

Immune-Mediated Colitis

  • Immune-mediated colitis or diarrhea have occurred with TECENTRIQ treatment
  • Across clinical trials, diarrhea or colitis occurred in 20% of patients, including Grade 3 (1.4%) events
  • Monitor patients for signs and symptoms of diarrhea or colitis. Withhold TECENTRIQ for Grade 2 or 3 and permanently discontinue for Grade 4 diarrhea or colitis

Immune-Mediated Endocrinopathies

  • TECENTRIQ can cause immune-mediated endocrinopathies, including thyroid disorders, adrenal insufficiency, and type 1 diabetes mellitus, including diabetic ketoacidosis, and hypophysitis/hypopituitarism
  • Withhold TECENTRIQ for Grade 2 to 4 endocrinopathies
  • Thyroid Disorders
    • Across clinical studies, hypothyroidism occurred in 4.6% of patients and hyperthyroidism occurred in 1.6% of patients
    • Monitor thyroid function prior to and during treatment with TECENTRIQ. Initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated
  • Adrenal Insufficiency
    • Across clinical studies, adrenal insufficiency occurred in 0.4% of patients, including Grade 3 (<0.1%) events
    • Monitor patients for clinical signs and symptoms of adrenal insufficiency. For Grade 2 to 4 adrenal insufficiency, initiate corticosteroids and hormone replacement therapy as clinically indicated
  • Type 1 Diabetes Mellitus
    • Across clinical studies, type 1 diabetes mellitus occurred in <0.1% of patients
    • Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated
  • Hypophysitis
    • Across clinical studies, Grade 2 hypophysitis occurred in <0.1% of patients
    • For Grade 2 to 4 hypophysitis, initiate corticosteroids and hormone replacement therapy as clinically indicated

Other Immune-Mediated Adverse Reactions

  • TECENTRIQ can cause severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system
  • Across clinical trials, cardiac, dermatologic, gastrointestinal, general, hematological, musculoskeletal, neurological, ophthalmological, renal, and vascular immune-mediated adverse reactions occurred at an incidence of <1% in patients who received TECENTRIQ or were reported for other products in this class of therapy
  • For suspected Grade 2 immune-mediated adverse reactions, exclude other causes and initiate corticosteroids as clinically indicated. For severe (Grade 3 or 4) adverse reactions, withhold TECENTRIQ and administer corticosteroids. Permanently discontinue TECENTRIQ for Grade 4 immune-mediated adverse reactions involving a major organ

Infections

  • TECENTRIQ can cause severe infections including fatal cases
  • Across clinical trials, infections occurred in 42% of patients, including Grade 3 (8.7%), Grade 4 (1.5%), and Grade 5 (1%) events
  • Monitor patients for signs and symptoms of infection. For Grade 3 or 4 infections, withhold TECENTRIQ and resume once clinically stable

Infusion-Related Reactions

  • TECENTRIQ can cause severe or life-threatening infusion-related reactions
  • Across clinical trials, infusion-related reactions occurred in 1.3% of patients, including Grade 3 (0.2%) events
  • Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2 infusion-related reactions. Permanently discontinue TECENTRIQ in patients with Grade 3 or 4 infusion-related reactions

Embryo-Fetal Toxicity

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

Nursing Mothers/Fertility

  • 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
  • Based on animal studies, TECENTRIQ may impair fertility in females of reproductive potential while receiving treatment

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 in previously treated UC (rate ≥20%) 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.