Cisplatin ineligible patient adverse events Cisplatin ineligible patient adverse events

INCIDENCE OF EACH ≥GRADE 3 IMMUNE-RELATED ADVERSE EVENT (AE) WAS <3% IN UROTHELIAL CARCINOMA TRIALS (n=523) 1

TECENTRIQ Adverse Events Profile TECENTRIQ Adverse Events Profile

ALT=alanine aminotransferase; AST=aspartate aminotransferase.
– indicates data not reported in Prescribing Information.

  • Across clinical trials
    • Immune-related adrenal insufficiency occurred in 0.4% of patients (7/1978)
    • Meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barré, ocular inflammatory toxicity, and pancreatitis, including increases in serum amylase and lipase levels, have occurred in ≤1% of patients treated with TECENTRIQ
  • In urothelial carcinoma (n=523)
    • 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
    • Severe infusion reactions occurred in 1.7% of patients
  • Immune-related AEs requiring systemic corticosteroids or hormone replacement therapy occurred in 19.3% of patients (23/119) in Cohort 1 and 11.0% of patients (34/310) in Cohort 2
    • 12.6% (15/119) in Cohort 1 and 8.4% (26/310) in Cohort 2 required systemic corticosteroid therapy; 6.7% (8/119) in Cohort 1 and 2.6% (8/310) in Cohort 2 required only hormone replacement therapy
    • Additionally, 5.0% (6/119) in Cohort 1 and 5.8% (18/310) in Cohort 2 received an oral prednisone dose equivalent to ≥40-mg daily for an immune-related AE

MOST OF THE COMMON AEs (≥10%) WERE GRADE 1 OR 2 IN COHORT 1 (n=119) 1

Cisplatin ineligible patient adverse events Cisplatin ineligible patient adverse events
  • The most common grade 3 or 4 AEs (≥2%) were fatigue, urinary tract infection, anemia, diarrhea, blood creatinine increase, intestinal obstruction, ALT increase, hyponatremia, decreased appetite, sepsis, back/neck pain, renal failure, and hypotension
  • 4.2% of patients (5/119) discontinued treatment due to an AE
    • AEs included diarrhea/colitis (1.7%), fatigue (0.8%), hypersensitivity (0.8%), and dyspnea (0.8%)
  • 35% of patients experienced AEs that led to interruptions of TECENTRIQ
    • The most common (≥1%) were intestinal obstruction, fatigue, diarrhea, urinary tract infection, infusion-related reaction, cough, abdominal pain, peripheral edema, pyrexia, respiratory tract infection, upper respiratory tract infection, creatinine increase, decreased appetite, hyponatremia, back pain, pruritus, and venous thromboembolism
  • 4.2% of patients (5/119) treated with TECENTRIQ experienced either sepsis, cardiac arrest, myocardial infarction, respiratory failure, or respiratory distress, which led to death. 0.8% of patients (1/119) experienced herpetic meningoencephalitis and disease progression at the time of death
  • 37% of patients experienced serious AEs
    • The most frequent (≥2%) were diarrhea, intestinal obstruction, sepsis, acute kidney injury, and renal failure

INCIDENCE OF GRADE 3 OR 4 LABORATORY ABNORMALITIES (≥1%) IN COHORT 1 (n=119) 1

Incidence of grade 3 or 4 laboratory abnormalities in IMvigor210 Incidence of grade 3 or 4 laboratory abnormalities in IMvigor210

ALT=alanine aminotransferase; AST=aspartate aminotransferase.

MOST OF THE COMMON AEs (≥10%) WERE GRADE 1 OR 2 IN COHORT 2 (n=310) 1

Previously treated patient adverse events Previously treated patient adverse events
  • The most common grade 3 or 4 AEs (≥2%) were urinary tract infection, anemia, fatigue, dehydration, intestinal obstruction, urinary obstruction, hematuria, dyspnea, acute kidney injury, abdominal pain, venous thromboembolism, sepsis, and pneumonia
  • 3.2% of patients (10/310) discontinued treatment due to an AE
    • Sepsis led to discontinuation in 0.6% of patients (2/310)
  • 27% of patients experienced AEs that led to interruptions of TECENTRIQ
    • The most common (>1%) were liver enzyme increase, urinary tract infection, diarrhea, fatigue, confusional state, urinary obstruction, pyrexia, dyspnea, venous thromboembolism, and pneumonitis
  • 1% of patients (3/310) treated with TECENTRIQ experienced either sepsis, pneumonitis, or intestinal obstruction, which led to death
  • 45% of patients experienced serious AEs
    • The most frequent (>2%) were urinary tract infection, hematuria, acute kidney injury, intestinal obstruction, pyrexia, venous thromboembolism, urinary obstruction, pneumonia, dyspnea, abdominal pain, sepsis, and confusional state

INCIDENCE OF GRADE 3 OR 4 LABORATORY ABNORMALITIES (≥1%) IN COHORT 2 (n=310) 1

Cohort 2 Lab ABs Cohort 2 Lab ABs

ALT=alanine aminotransferase; AST=aspartate aminotransferase.

IMPORTANT SAFETY INFORMATION AND INDICATION

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.

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.