Tecentriq® (atezolizumab)

Side Effect Reporting

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.

You may also report side effects to Genentech at (888) 835-2555.

Indication

Locally Advanced or Metastatic Urothelial Carcinoma

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.

Metastatic Non-Small Cell Lung Cancer

TECENTRIQ is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving TECENTRIQ.

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, defined as requiring use of corticosteroids and with no clear alternate etiology, occurred in patients receiving TECENTRIQ. Monitor patients for signs with radiographic imaging and symptoms of pneumonitis. Administer steroids at a dose of 1 to 2 mg/kg/day prednisone equivalents for Grade 2 or greater pneumonitis, followed by corticosteroid taper. Withhold TECENTRIQ until resolution for Grade 2 pneumonitis. Permanently discontinue TECENTRIQ for Grade 3 or 4 pneumonitis
  • Across clinical trials, 2.6% of patients developed pneumonitis. Fatal pneumonitis occurred in 2 patients

Urothelial Carcinoma

  • In 523 patients with urothelial carcinoma (UC) who received TECENTRIQ, pneumonitis occurred in 6 (1.1%) patients. Of these patients, there was 1 patient with fatal pneumonitis, 1 patient with Grade 3, three with Grade 2, and 1 patient with Grade 1 pneumonitis. TECENTRIQ was held in all cases and 5 patients were treated with corticosteroids. Pneumonitis resolved in 3 patients

NSCLC

  • In 1027 patients with non-small cell lung cancer (NSCLC) who received TECENTRIQ, pneumonitis occurred in 38 (3.7%) patients. Of these patients, there was 1 patient with fatal pneumonitis, 2 patients with Grade 4, thirteen with Grade 3, eleven with Grade 2, and 11 patients with Grade 1 pneumonitis. TECENTRIQ was held in 24 patients and 21 patients were treated with corticosteroids. Pneumonitis resolved in 26 patients

Immune-Related Hepatitis

  • Immune-mediated hepatitis, defined as requiring use of corticosteroids and with no clear alternate etiology, occurred in patients receiving TECENTRIQ treatment. Liver test abnormalities occurred in patients who received TECENTRIQ. Monitor patients for signs and symptoms of hepatitis. Monitor AST, ALT, and bilirubin prior to and periodically during treatment with TECENTRIQ. Administer corticosteroids at a dose of 1-2 mg/kg/day prednisone equivalents for Grade 2 or greater transaminase elevations, with or without concomitant elevation in total bilirubin, followed by corticosteroid taper. Withhold TECENTRIQ for Grade 2 and permanently discontinue TECENTRIQ for Grade 3 or 4 immune-mediated hepatitis
  • Across clinical trials, Grade 3 or 4 elevation occurred in ALT (2.5%), AST (2.3%), and total bilirubin (1.6%)

Urothelial Carcinoma

  • In patients with UC, Grade 3 or 4 elevation occurred in ALT (2.5%), AST (2.5%), and total bilirubin (2.1%). Immune-mediated hepatitis occurred in 1.3% of patients, including a fatal case. Of these cases, 1 patient died from hepatitis, 5 patients had Grade 3, and 1 patient had Grade 2 hepatitis. TECENTRIQ was temporarily interrupted in 4 patients; none of these patients developed recurrence of hepatitis after resuming TECENTRIQ

NSCLC

  • In patients with NSCLC, Grade 3 or 4 elevation occurred in ALT (1.4%), AST (1.3%), and total bilirubin (0.6%). Immune-mediated hepatitis occurred in 0.9% of patients. Of these 9 patients, 1 patient had Grade 4, four patients had Grade 3, three had Grade 2, and 1 patient had Grade 1 immune-mediated hepatitis. TECENTRIQ was temporarily interrupted in 7 patients; none of these patients developed recurrence of hepatitis after resuming TECENTRIQ

Immune-Related Colitis

  • Immune-mediated colitis or diarrhea, defined as requiring use of corticosteroids and with no clear alternate etiology, occurred in patients receiving TECENTRIQ. Monitor patients for signs and symptoms of diarrhea or colitis. Withhold treatment with TECENTRIQ for Grade 2 diarrhea or colitis. If symptoms persist longer than 5 days or recur, administer 1-2 mg/kg prednisone or equivalent per day. Withhold treatment with TECENTRIQ for Grade 3 diarrhea or colitis. Treat with IV methylprednisolone 1-2 mg/kg per day and convert to oral steroids once the patient has improved. For both Grade 2 and Grade 3 diarrhea or colitis, when symptoms improve to Grade 0 or Grade 1, taper steroids over ≥1 month. Resume treatment with TECENTRIQ if the event improves to Grade 0 or 1 within 12 weeks and corticosteroids have been reduced to the equivalent of ≤10 mg oral prednisone per day. Permanently discontinue TECENTRIQ for Grade 4 diarrhea or colitis
  • Across clinical trials, colitis or diarrhea occurred in 19.7% of all patients

Urothelial Carcinoma

  • In 523 patients with UC who received TECENTRIQ, colitis or diarrhea occurred in 18.7% of patients. Ten patients (1.9%) developed Grade 3 or 4 diarrhea. Four patients (0.8%) had immune-mediated colitis or diarrhea. Immune-mediated colitis resolved with corticosteroid administration in 3 of these patients, while the other patient died without resolution of colitis in the setting of diarrhea-associated renal failure

NSCLC

  • In 1027 patients with NSCLC who received TECENTRIQ, colitis or diarrhea occurred in 19.3% of patients. Twelve patients (1.2%) developed Grade 3 colitis or diarrhea. Five patients (0.5%) had immune-mediated colitis or diarrhea. Immune-mediated colitis or diarrhea resolved with corticosteroid administration in 4 of these patients, while the fifth patient died due to disease progression prior to resolution of 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

Hypophysitis

  • Hypophysitis occurred in 0.2% of patients with urothelial cancer receiving TECENTRIQ. Monitor for signs and symptoms of hypophysitis. Administer corticosteroids and hormone replacement as clinically indicated. Withhold TECENTRIQ for Grade 2 or Grade 3, and permanently discontinue for Grade 4 hypophysitis

Thyroid Disorders

  • Thyroid function was assessed routinely only at baseline and the end of the study. Monitor thyroid function prior to and periodically during treatment with TECENTRIQ. Asymptomatic patients with abnormal thyroid function tests can receive TECENTRIQ. For symptomatic hypothyroidism, withhold TECENTRIQ and initiate thyroid hormone replacement as needed. Manage isolated hypothyroidism with replacement therapy and without corticosteroids. For symptomatic hyperthyroidism, withhold TECENTRIQ and initiate an antithyroid drug as needed. Resume treatment with TECENTRIQ when symptoms of hypothyroidism or hyperthyroidism are controlled and thyroid function is improving
  • Across clinical trials, hypothyroidism and hyperthyroidism occurred in 3.9% and 1.0% of patients, respectively

Urothelial Carcinoma

  • In 523 patients with UC who received TECENTRIQ, hypothyroidism occurred in 2.5%. Thyroid stimulating hormone (TSH) was elevated and above the patient’s baseline in 16% of patients with a follow-up measurement
  • Hyperthyroidism occurred in 0.6% of patients with UC. TSH was decreased and below the patient’s baseline in 3.8% of patients with a follow-up measurement

NSCLC

  • In 1027 patients with NSCLC who received TECENTRIQ, hypothyroidism occurred in 4.2%. TSH was elevated and above the patient’s baseline in 17% of patients with follow-up measurement
  • Hyperthyroidism occurred in 1.1% of patients with NSCLC. TSH was decreased and below the patient’s baseline in 7.6% of patients with a follow-up measurement

Adrenal Insufficiency

  • Adrenal insufficiency occurred in 0.4% of patients across clinical trials
  • For symptomatic adrenal insufficiency, withhold TECENTRIQ and administer methylprednisolone 1-2 mg/kg per day IV, followed by oral prednisone 1-2 mg/kg per day or equivalent once symptoms improve. Start steroid taper when symptoms improve to ≤Grade 1 and taper steroids over ≥1 month. Resume treatment with TECENTRIQ if the event improves to ≤Grade 1 within 12 weeks and corticosteroids have been reduced to the equivalent of ≤10 mg oral prednisone per day and the patient is stable on replacement therapy, if required

Diabetes Mellitus

  • New onset diabetes with ketoacidosis has occurred in patients receiving TECENTRIQ. Diabetes mellitus without an alternative etiology occurred in 0.2% of patients with UC and 0.3% of patients with NSCLC
  • Initiate treatment with insulin for type 1 diabetes mellitus. For ≥Grade 3 hyperglycemia (fasting glucose >250-500 mg/dL), withhold TECENTRIQ. Resume treatment with TECENTRIQ when metabolic control is achieved on insulin replacement therapy

Other Immune-Related Adverse Reactions

  • Other immune-related adverse reactions, including meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barré, ocular inflammatory toxicity, and pancreatitis, including increases in serum amylase and lipase levels, have occurred in ≤1.0% of patients treated with TECENTRIQ

Meningitis/Encephalitis

  • Monitor patients for clinical signs and symptoms of meningitis or encephalitis. Permanently discontinue TECENTRIQ for any grade of meningitis or encephalitis. Treat with IV steroids (1-2 mg/kg/day methylprednisolone or equivalent) and convert to oral steroids (prednisone 60 mg/day or equivalent) once the patient has improved. When symptoms improve to ≤Grade 1, taper steroids over ≥1 month

Motor and Sensory Neuropathy

  • Monitor patients for symptoms of motor and sensory neuropathy. Permanently discontinue TECENTRIQ for any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome. Institute medical intervention as appropriate. Consider initiation of systemic corticosteroids at a dose of 1-2 mg/kg/day prednisone

Pancreatitis

  • Symptomatic pancreatitis without an alternative etiology occurred in 0.1% of patients across clinical trials
  • 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. Treat with 1-2 mg/kg IV methylprednisolone or equivalent per day. Once symptoms improve, follow with 1-2 mg/kg of oral prednisone or equivalent per day. Resume treatment with TECENTRIQ when serum amylase and lipase levels improve to ≤Grade 1 within 12 weeks or symptoms of pancreatitis have resolved, and corticosteroids have been reduced to ≤10 mg oral prednisone or equivalent per day
  • Permanently discontinue TECENTRIQ 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. Monitor patients for signs and symptoms of infection and treat with antibiotics for suspected or confirmed bacterial infections. Withhold TECENTRIQ for ≥Grade 3 infection
  • Across clinical trials, infections occurred in 38.4% of patients

Urothelial Carcinoma

  • In 523 patients with UC who received TECENTRIQ, 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

NSCLC

  • In Study 3, a randomized trial in patients with NSCLC, infections were more common in patients treated with TECENTRIQ (43%) compared with those treated with docetaxel (34%). Grade 3 or 4 infections occurred in 9.2% of patients treated with TECENTRIQ compared with 2.2% in patients treated with docetaxel. Two patients (1.4%) treated with TECENTRIQ, and 3 patients (2.2%) treated with docetaxel died due to infection. Pneumonia was the most common cause of Grade 3 or higher infection, occurring in 7.7% of patients treated with TECENTRIQ

Infusion-Related Reactions

  • Severe infusion reactions have occurred in patients in clinical trials of TECENTRIQ. Infusion-related reactions occurred in 1.3% of patients across clinical trials, 1.7% of patients with UC, and 1.6% of patients with NSCLC. 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. Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus, resulting in fetal death
  • If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient 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

Use In Specific Populations

Nursing Mothers

  • There is no information regarding the presence of TECENTRIQ in human milk, the effects on the breastfed infant, or the effects on milk production. As human IgG is excreted in human milk, the potential for absorption and harm to the infant is unknown
  • Advise female patients not to breastfeed while taking TECENTRIQ and for at least 5 months after the last dose

Fertility

  • 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 (rate ≥20%) in cisplatin-ineligible UC were fatigue (52%), decreased appetite (24%), diarrhea (24%), and nausea (22%). Serious adverse reactions occurred in 37% of patients. The most frequent serious adverse reactions (≥2%) were diarrhea, intestinal obstruction, sepsis, acute kidney injury, and renal failure.

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%). Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions (>2%) were urinary tract infection, hematuria, acute kidney injury, intestinal obstruction, pyrexia, venous thromboembolism, urinary obstruction, pneumonia, dyspnea, abdominal pain, sepsis, and confusional state.

The most common adverse reactions in NSCLC (rate ≥20%) included fatigue (46%), decreased appetite (35%), dyspnea (32%), cough (30%), nausea (22%), musculoskeletal pain (22%), and constipation (20%). Serious adverse reactions occurred in 37% of patients. The most frequent serious adverse reactions (>2%) were pneumonia, dyspnea, pleural effusion, pyrexia, and venous thromboembolism.

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 [accompanying] full Prescribing Information for additional Important Safety Information.