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Tecentriq

Last reviewed on RxList: 2/24/2021
Tecentriq Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Tecentriq?

Tecentriq (atezolizumab) Injection for intravenous infusion is a monoclonal antibody indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (cancer) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

What Are Side Effects of Tecentriq?

Common side effects of Tecentriq include:

Dosage for Tecentriq

The recommended dose of Tecentriq is 1200 mg administered as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.

What Drugs, Substances, or Supplements Interact with Tecentriq?

Tecentriq may interact with other drugs. Tell your doctor all medications and supplements you use.

Tecentriq During Pregnancy and Breastfeeding

Tecentriq is not recommended during pregnancy; it may harm a fetus. Breastfeeding is not recommended while taking Tecentriq and for at least 5 months after the last dose.

Additional Information

Our Tecentriq (atezolizumab) Injection for Intravenous Infusion Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Prostate Cancer Symptoms, PCA Test, Treatments See Slideshow
Tecentriq Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, light-headed, chilled or feverish, itchy, tingly, or have neck or back pain, trouble breathing, or swelling in your face.

Call your doctor at once if you have:

  • new or worsening cough, shortness of breath;
  • chest pain, irregular heartbeats;
  • swelling in your ankles;
  • severe stomach pain, nausea, vomiting, diarrhea, bloody or tarry stools;
  • liver problems--right-sided upper stomach pain, loss of appetite, drowsiness, easy bruising or bleeding, dark urine, jaundice (yellowing of the skin or eyes);
  • nervous system problems--neck stiffness, increased sensitivity to light, confusion, severe muscle weakness, numbness or tingling in your hands or feet, vision problems, eye pain or redness;
  • low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet;
  • signs of infection--fever, flu symptoms, cough, back pain, painful or frequent urination; or
  • signs of a hormonal disorder--frequent or unusual headaches, extreme tiredness, dizziness or fainting, mood or behavior changes, hoarse or deepened voice, increased hunger or thirst, increased urination, constipation, hair loss, feeling cold, weight gain, or weight loss.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • nausea, vomiting, loss of appetite;
  • diarrhea, constipation;
  • anemia, infections;
  • cough, feeling short of breath;
  • liver problems;
  • mouth sores or swelling;
  • high blood pressure, abnormal blood or urine tests;
  • headache, tiredness, weakness
  • joint, muscle, or bone pain;
  • numbness or tingling in your hands or feet;
  • swelling in your legs or arms;
  • rash, itching, sunburn or being more sensitive to sunlight; or
  • hair loss.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Tecentriq (Atezolizumab Injection)

Tecentriq Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Severe and Fatal Immune-Mediated Adverse Reactions [see WARNINGS AND PRECAUTIONS]
  • Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described in WARNINGS AND PRECAUTIONS reflect exposure to TECENTRIQ as a single-agent in 2616 patients in two randomized, active-controlled studies (POPLAR, OAK) and four open-label, single arm studies (PCD4989g, IMvigor210, BIRCH, FIR) which enrolled 524 patients with metastatic urothelial carcinoma, 1636 patients with metastatic NSCLC, and 456 patients with other tumor types. TECENTRIQ was administered at a dose of 1200 mg intravenously every 3 weeks in all studies except PCD4989g. Among the 2616 patients who received a single-agent TECENTRIQ, 36% were exposed for longer than 6 months and 20% were exposed for longer than 12 months. Using the dataset described for patients who received TECENTRIQ as a single-agent, the most common adverse reactions in ≥ 20% of patients were fatigue/asthenia (48%), decreased appetite (25%), nausea (24%), cough (22%), and dyspnea (22%).

In addition, the data reflect exposure to TECENTRIQ in combination with other antineoplastic drugs in 2421 patients with NSCLC (N = 2223) or SCLC (N = 198) enrolled in five randomized, active-controlled trials, including IMpower150, IMpower130 and IMpower133. Among the 2421 patients, 53% were exposed to TECENTRIQ for longer than 6 months and 29% were exposed to TECENTRIQ for longer than 12 months. Among the 2421 patients with NSCLC and SCLC who received TECENTRIQ in combination with other antineoplastic drugs, the most common adverse reactions in ≥20% of patients were fatigue/asthenia (49%), nausea (38%), alopecia (35%), constipation (29%), diarrhea (28%) and decreased appetite (27%).

The data also reflect exposure to TECENTRIQ administered in combination with cobimetinib and vemurafenib in 230 patients enrolled in IMspire150. Among the 230 patients, 62% were exposed to TECENTRIQ for longer than 6 months and 42% were exposed to TECENTRIQ for longer than 12 months.

Urothelial Carcinoma

Cisplatin-Ineligible Patients with Locally Advanced or Metastatic Urothelial Carcinoma

The safety of TECENTRIQ was evaluated in IMvigor 210 (Cohort 1), a multicenter, open-label, single-arm trial that included 119 patients with locally advanced or metastatic urothelial carcinoma who were ineligible for cisplatin-containing chemotherapy and were either previously untreated or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy [see Clinical Studies]. Patients received TECENTRIQ 1200 mg intravenously every 3 weeks until either unacceptable toxicity or disease progression. The median duration of exposure was 15 weeks (0 to 87 weeks).

Five patients (4.2%) who were treated with TECENTRIQ experienced one of the following events which led to death: sepsis, cardiac arrest, myocardial infarction, respiratory failure, or respiratory distress. One additional patient (0.8%) was experiencing herpetic meningoencephalitis and disease progression at the time of death.

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.

TECENTRIQ was discontinued for adverse reactions in 4.2% of patients. The adverse reactions leading to discontinuation were diarrhea/colitis (1.7%), fatigue (0.8%), hypersensitivity (0.8%), and dyspnea (0.8%).

Adverse reactions leading to interruption occurred in 35% of patients; 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.

Tables 2 and 3 summarize the adverse reactions and Grades 3–4 selected laboratory abnormalities, respectively, in patients who received TECENTRIQ in IMvigor210 (Cohort 1).

Table 2: Adverse Reactions in ≥ 10% of Patients with Urothelial Carcinoma in IMvigor210 (Cohort 1)

Adverse ReactionTECENTRIQ
N = 119
All Grades
(%)
Grades 3–4
(%)
General
Fatigue1528
Peripheral edema2172
Pyrexia140.8
Gastrointestinal
Diarrhea3245
Nausea222
Vomiting160.8
Constipation152
Abdominal pain4150.8
Metabolism and Nutrition
Decreased appetite5243
Musculoskeletal and Connective Tissue
Back/Neck pain183
Arthralgia130
Skin and Subcutaneous Tissue
Pruritus180.8
Rash6170.8
Infections
Urinary tract infection7175
Respiratory, Thoracic, and Mediastinal
Cough8140
Dyspnea9120
1 Includes fatigue, asthenia, lethargy, and malaise
2 Includes edema peripheral, scrotal edema, lymphedema, and edema
3 Includes diarrhea, colitis, frequent bowel movements, autoimmune colitis
4 Includes abdominal pain, upper abdominal pain, lower abdominal pain, and flank pain
5 Includes decreased appetite and early satiety
6 Includes rash, dermatitis, dermatitis acneiform, rash maculo-papular, rash erythematous, rash pruritic, rash macular, and rash papular
7 Includes urinary tract infection, urinary tract infection bacterial, cystitis, and urosepsis
8 Includes cough and productive cough
9 Includes dyspnea and exertional dyspnea

Table 3: Grades 3–4 Laboratory Abnormalities in ≥ 1% of Patients with Urothelial Carcinoma in IMvigor210 (Cohort 1)

Laboratory AbnormalityGrades 3–4
(%)
Chemistry
Hyponatremia15
Hyperglycemia10
Increased Alkaline Phosphatase7
Increased Creatinine5
Hypophosphatemia4
Increased ALT4
Increased AST4
Hyperkalemia3
Hypermagnesemia3
Hyperbilirubinemia3
Hematology
Lymphopenia9
Anemia7
Graded per NCI CTCAE v4.0.

Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma

The safety of TECENTRIQ was evaluated in IMvigor210 (Cohort 2), a multicenter, open-label, single-arm trial that included 310 patients with locally advanced or metastatic urothelial carcinoma who had disease progression during or following at least one platinum-containing chemotherapy regimen or who had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen [see Clinical Studies]. Patients received TECENTRIQ 1200 mg intravenously every 3 weeks until unacceptable toxicity or either radiographic or clinical progression. The median duration of exposure was 12.3 weeks (0.1 to 46 weeks).

Three patients (1%) who were treated with TECENTRIQ experienced one of the following events which led to death: sepsis, pneumonitis, or intestinal obstruction.

TECENTRIQ was discontinued for adverse reactions in 3.2% of patients. Sepsis led to discontinuation in 0.6% of patients.

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.

Adverse reactions leading to interruption occurred in 27% of patients; the most common (> 1%) were liver enzyme increase, urinary tract infection, diarrhea, fatigue, confusional state, urinary obstruction, pyrexia, dyspnea, venous thromboembolism, and pneumonitis.

Tables 4 and 5 summarize the adverse reactions and Grades 3–4 selected laboratory abnormalities, respectively, in patients who received TECENTRIQ in IMvigor210 (Cohort 2).

Table 4: Adverse Reactions in ≥ 10% of Patients with Urothelial Carcinoma in IMvigor210 (Cohort 2)

Adverse ReactionTECENTRIQ
N = 310
All Grades
(%)
Grades 3–4
(%)
General
Fatigue526
Pyrexia211
Peripheral edema181
Metabolism and Nutrition
Decreased appetite261
Gastrointestinal
Nausea252
Constipation210.3
Diarrhea181
Abdominal pain174
Vomiting171
Infections
Urinary tract infection229
Respiratory, Thoracic, and Mediastinal
Dyspnea164
Cough140.3
Musculoskeletal and Connective Tissue
Back/Neck pain152
Arthralgia141
Skin and Subcutaneous Tissue
Rash150.3
Pruritus130.3
Renal and Urinary
Hematuria143

Table 5: Grades 3–4 Laboratory Abnormalities in ≥ 1% of Patients with Urothelial Carcinoma in IMvigor210 (Cohort 2)

Laboratory AbnormalityGrades 3–4
(%)
Chemistry
Hyponatremia10
Hyperglycemia5
Increased Alkaline Phosphatase4
Increased Creatinine3
Increased ALT2
Increased AST2
Hypoalbuminemia1
Hematology
Lymphopenia10
Anemia8
Graded per NCI CTCAE v4.0.

Non-Small Cell Lung Cancer (NSCLC)

IMpower110

The safety of TECENTRIQ was evaluated in IMpower110, a multicenter, international, randomized, open-label study in 549 chemotherapy-naïve patients with stage IV NSCLC, including those with EGFR or ALK genomic tumor aberrations. Patients received TECENTRIQ 1200 mg every 3 weeks (n=286) or platinum-based chemotherapy consisting of carboplatin or cisplatin with either pemetrexed or gemcitabine (n=263) until disease progression or unacceptable toxicity [see Clinical Studies]. IMpower110 enrolled patients whose tumors express PD-L1 (PD-L1 stained ≥ 1% of tumor cells [TC] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 1% of the tumor area). The median duration of exposure to TECENTRIQ was 5.3 months (0 to 33 months).

Fatal adverse reactions occurred in 3.8% of patients receiving TECENTRIQ; these included death (reported as unexplained death and death of unknown cause), aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (1 patient each).

Serious adverse reactions occurred in 28% of patients receiving TECENTRIQ. The most frequent serious adverse reactions (>2%) were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%) and pneumonitis (2.1%)

TECENTRIQ was discontinued due to adverse reactions in 6% of patients; the most common adverse reactions (≥2 patients) leading to TECENTRIQ discontinuation were peripheral neuropathy and pneumonitis.

Adverse reactions leading to interruption of TECENTRIQ occurred in 26% of patients; the most common (>1%) were ALT increased (2.1%), AST increased (2.1%), pneumonitis (2.1%), pyrexia (1.4%), pneumonia (1.4%) and upper respiratory tract infection (1.4%).

Tables 6 and 7 summarize adverse reactions and selected laboratory abnormalities in patients receiving TECENTRIQ in IMpower110.

Table 6: Adverse Reactions Occurring in ≥10% of Patients with NSCLC Receiving TECENTRIQ in IMpower110

Adverse ReactionTECENTRIQ
N = 286
Platinum-Based Chemotherapy
N = 263
All Grades
(%)
Grades 3–4*
(%)
All Grades*
(%)
Grades 3–4
(%)
Gastrointestinal
Nausea140.3341.9
Constipation121.0220.8
Diarrhea110120.8
General
Fatigue/asthenia251.4344.2
Pyrexia14090.4
Metabolism and Nutrition
Decreased appetite150.7190
Respiratory, Thoracic and Mediastinal
Dyspnea140.7100
Cough120.3100
Graded per NCI CTCAE v4.0

Table 7: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients Receiving TECENTRIQ in IMpower110

Laboratory AbnormalityTECENTRIQPlatinum Based Chemotherapy
All Grades
(%)
Grades 3–4
(%)
All Grades
(%)
Grades 3–4
(%)
Hematology
Anemia691.89420
Lymphopenia4795917
Chemistry
Hypoalbuminemia480.4392
Increased alkaline phosphatase462.5421.2
Hyponatremia449367
Increased ALT383.2320.8
Increased AST363.2320.8
Hyperkalemia293.9362.7
Hypocalcemia241.4242.7
Increased blood creatinine240.7331.5
Hypophosphatemia233.6212
Each test incidence is based on the number of patients who had at least one on-study laboratory measurement available: TECENTRIQ (range: 278-281); platinum-based chemotherapy (range:256-260). Graded per NCI CTCAE v4.0. Increased blood creatinine only includes patients with test results above the normal range.

IMpower150

The safety of TECENTRIQ with bevacizumab, paclitaxel and carboplatin was evaluated in IMpower150, a multicenter, international, randomized, open-label trial in which 393 chemotherapy-naïve patients with metastatic non-squamous NSCLC received TECENTRIQ 1200 mg with bevacizumab 15 mg/kg, paclitaxel 175 mg/m2 or 200 mg/m2, and carboplatin AUC 6 mg/mL/min intravenously every 3 weeks for a maximum of 4 or 6 cycles, followed by TECENTRIQ 1200 mg with bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity [see Clinical Studies]. The median duration of exposure to TECENTRIQ was 8.3 months in patients receiving TECENTRIQ with bevacizumab, paclitaxel, and carboplatin.

Fatal adverse reactions occurred in 6% of patients receiving TECENTRIQ; these included hemoptysis, febrile neutropenia, pulmonary embolism, pulmonary hemorrhage, death, cardiac arrest, cerebrovascular accident, pneumonia, aspiration pneumonia, chronic obstructive pulmonary disease, intracranial hemorrhage, intestinal angina, intestinal ischemia, intestinal obstruction and aortic dissection.

Serious adverse reactions occurred in 44%. The most frequent serious adverse reactions (>2%) were febrile neutropenia, pneumonia, diarrhea, and hemoptysis.

TECENTRIQ was discontinued due to adverse reactions in 15% of patients; the most common adverse reaction leading to discontinuation was pneumonitis (1.8%).

Adverse reactions leading to interruption of TECENTRIQ occurred in 48%; the most common (>1%) were neutropenia, thrombocytopenia, fatigue/asthenia, diarrhea, hypothyroidism, anemia, pneumonia, pyrexia, hyperthyroidism, febrile neutropenia, increased ALT, dyspnea, dehydration and proteinuria.

Tables 8 and 9 summarize adverse reactions and laboratory abnormalities in patients receiving TECENTRIQ with bevacizumab, paclitaxel, and carboplatin in IMpower150.

Table 8: Adverse Reactions Occurring in ≥15% of Patients with NSCLC Receiving TECENTRIQ in IMpower150

Adverse ReactionTECENTRIQ with Bevacizumab, Paclitaxel, and Carboplatin
N = 393
Bevacizumab, Paclitaxel and Carboplatin
N = 394
All Grades
(%)
Grades 3–4
(%)
All Grades
(%)
Grades 3–4
(%)
Nervous System
Neuropathy1563473
Headache160.8130
General
Fatigue/Asthenia506466
Pyrexia190.390.5
Skin and Subcutaneous Tissue
Alopecia480460
Rash2232100.3
Musculoskeletal and Connective Tissue
Myalgia/Pain3423342
Arthralgia261221
Gastrointestinal
Nausea394322
Diarrhea4336250.5
Constipation300.3230.3
Vomiting192181
Metabolism and Nutrition
Decreased appetite294210.8
Vascular
Hypertension259228
Respiratory
Cough200.8190.3
Epistaxis171220.3
Renal
Proteinuria5163153
Graded per NCI CTCAE v4.0
1 Includes neuropathy peripheral, peripheral sensory neuropathy, hypoesthesia, paraesthesia, dysesthesia, polyneuropathy.
2 Includes rash, rash maculo-papular, drug eruption, eczema, eczema asteatotic, dermatitis, contact dermatitis, rash erythematous, rash macular, pruritic rash, seborrheic dermatitis, dermatitis psoriasiform.
3 Includes pain in extremity, musculoskeletal chest pain, musculoskeletal discomfort, neck pain, backpain, myalgia, and bone pain.
4 Includes diarrhea, gastroenteritis, colitis, enterocolitis.
5 Data based on Preferred Terms since laboratory data for proteinuria were not systematically collected.

Table 9: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients with NSCLC Receiving TECENTRIQ in IMpower150

Laboratory AbnormalityTECENTRIQ with Bevacizumab, Paclitaxel, and CarboplatinBevacizumab, Paclitaxel and Carboplatin
All Grades
(%)
Grades 3–4
(%)
All Grades
(%)
Grades 3–4
(%)
Hematology
Anemia8310839
Neutropenia52314526
Lymphopenia48173813
Chemistry
Hyperglycemia610600
Increased BUN52NA144NA1
Hypomagnesemia422361
Hypoalbuminemia403312
Increased AST404280.8
Hyponatremia3810369
Increased Alkaline Phosphatase372321
Increased ALT376280.5
Increased TSH30NA120NA1
Hyperkalemia283252
Increased Creatinine281192
Hypocalcemia263213
Hypophosphatemia254184
Hypokalemia237144
Hyperphosphatemia25NA119NA1
Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: TECENTRIQ with bevacizumab, paclitaxel, and carboplatin range: 337-380); bevacizumab, paclitaxel, and carboplatin (range: 337-382). Graded per NCI CTCAE v4.0
1 NA = Not applicable. NCI CTCAE does not provide a Grades 3-4 definition for these laboratory abnormalities

IMpower130

The safety of TECENTRIQ with paclitaxel protein-bound and carboplatin was evaluated in IMpower130, a multicenter, international, randomized, open-label trial in which 473 chemotherapy-naïve patients with metastatic non-squamous NSCLC received TECENTRIQ 1200 mg and carboplatin AUC 6 mg/mL/min intravenously on Day 1 and paclitaxel protein-bound 100 mg/m2 intravenously on Day 1, 8, and 15 of each 21-day cycle for a maximum of 4 or 6 cycles, followed by TECENTRIQ 1200 mg intravenously every 3 weeks until disease progression or unacceptability toxicity [see Clinical Studies]. Among patients receiving TECENTRIQ, 55% were exposed for 6 months or longer and 3.5% were exposed for greater than one year.

Fatal adverse reactions occurred in 5.3% of patients receiving TECENTRIQ; these included including pneumonia (1.1%), pulmonary embolism (0.8%), myocardial infarction (0.6%), cardiac arrest (0.4%) and pneumonitis (0.4%) and sepsis, septic shock, staphylococcal sepsis, aspiration, respiratory distress, cardiorespiratory arrest, ventricular tachycardia, death (not otherwise specified), and hepatic cirrhosis (0.2% each).

Serious adverse reactions occurred in 51% of patients receiving TECENTRIQ. The most frequent serious adverse reactions (≥2%) were pneumonia (6%), diarrhea (3%), lung infection (3.0%), pulmonary embolism (3%), chronic obstructive pulmonary disease exacerbation (2.5%), dyspnea (2.3%), and febrile neutropenia (1.9%).

TECENTRIQ was discontinued due to adverse reactions in 13% of patients; the most common adverse reactions leading to discontinuation were pneumonia (0.8%), pulmonary embolism (0.8%), fatigue (0.6%), dyspnea (0.6%), pneumonitis (0.6%), neutropenia (0.4%), nausea (0.4%), renal failure (0.4%), cardiac arrest (0.4%), and septic shock (0.4%).

Adverse reactions leading to interruption of TECENTRIQ occurred in 62% of patients; the most common (>1%) were neutropenia, thrombocytopenia, anemia, diarrhea, fatigue/asthenia, pneumonia, dyspnea, pneumonitis, pyrexia, nausea, acute kidney injury, vomiting, pulmonary embolism, arthralgia, infusion-related reaction, abdominal pain, chronic obstructive pulmonary disease exacerbation, dehydration, and hypokalemia.

Tables 10 and 11 summarize adverse reactions and laboratory abnormalities in patients receiving TECENTRIQ with paclitaxel protein-bound and carboplatin in IMpower130.

Table 10: Adverse Reactions Occurring in ≥20% of Patients with NSCLC Receiving TECENTRIQ in IMpower130

Adverse ReactionTECENTRIQ with Paclitaxel Protein-Bound and Carboplatin
N = 473
Paclitaxel Protein-Bound and Carboplatin
N = 232
All Grades
(%)
Grades 3–4
(%)
All Grades
(%)
Grades 3–4
(%)
General
Fatigue/Asthenia6111608
Gastrointestinal
Nausea503.4462.2
Diarrhea 1436326
Constipation361.1310
Vomiting272.7192.2
Musculoskeletal and Connective Tissue
Myalgia/Pain 2383220.4
Nervous System
Neuropathy 3332.5282.2
Respiratory, Thoracic and Mediastinal
Dyspnea 4324.9251.3
Cough270.6170
Skin and Subcutaneous Tissue
Alopecia320270
Rash 5200.6110.9
Metabolism and Nutrition
Decreased appetite302.1262.2
Graded per NCI CTCAE v4.0
1 Includes diarrhea, colitis, and gastroenteritis
2 Includes back pain, pain in extremity, myalgia, musculoskeletal chest pain, bone pain, neck pain and musculoskeletal discomfort
3 Includes neuropathy peripheral, peripheral sensory neuropathy, hypoesthesia, paresthesia, dysesthesia, polyneuropathy
4 Includes dyspnea, dyspnea exertional and wheezing
5 Includes rash, rash maculo-papular, eczema, rash pruritic, rash erythematous, dermatitis, dermatitis contact, drug eruption, seborrheic dermatitis and rash macular.

Table 11: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients Receiving TECENTRIQ in IMpower130

Laboratory AbnormalityTECENTRIQ with Paclitaxel Protein-Bound and Carboplatin
N = 473
Paclitaxel Protein-Bound and Carboplatin
N = 232
All Grades
(%)
Grades 3–4
(%)
All Grades
(%)
Grades 3–4
(%)
Hematology
Anemia92338725
Neutropenia75506739
Thrombocytopenia73195913
Lymphopenia71236116
Chemistry
Hyperglycemia758668
Hypomagnesemia503.4423.2
Hyponatremia379287
Hypoalbuminemia351.3310
Increased ALT312.8243.9
Hypocalcemia312.6271.8
Hypophosphatemia296203.2
Increased AST282.2241.8
Increased TSH26NA15NA1
Hypokalemia266244.4
Increased Alkaline Phosphatase252.6221.3
Increased Blood Creatinine232.8160.4
Hyperphosphatemia21NA113NA1
Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: TECENTRIQ with paclitaxel protein bound and carboplatin (range: 423 -467); paclitaxel protein bound and carboplatin (range: 218-229). Graded per NCI CTCAE v4.0.
1 NA = Not applicable. NCI CTCAE does not provide a Grades 3-4 definition for these laboratory abnormalities

Previously Treated Metastatic NSCLC

The safety of TECENTRIQ was evaluated in OAK, a multicenter, international, randomized, open-label trial in patients with metastatic NSCLC who progressed during or following a platinum-containing regimen, regardless of PD-L1 expression [see Clinical Studies].A total of 609 patients received TECENTRIQ 1200 mg intravenously every 3 weeks until unacceptable toxicity, radiographic progression, or clinical progression or docetaxel (n=578) 75 mg/m2 intravenously every 3 weeks until unacceptable toxicity or disease progression. The study excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids. The median duration of exposure was 3.4 months (0 to 26 months) in TECENTRIQ-treated patients and 2.1 months (0 to 23 months) in docetaxel-treated patients.

The study population characteristics were: median age of 63 years (25 to 85 years), 46% age 65 years or older, 62% male, 71% White, 20% Asian, 68% former smoker, 16% current smoker, and 63% had ECOG performance status of 1.

Fatal adverse reactions occurred in 1.6% of patients; these included pneumonia, sepsis, septic shock, dyspnea, pulmonary hemorrhage, sudden death, myocardial ischemia or renal failure.

Serious adverse reactions occurred in 33.5% of patients. The most frequent serious adverse reactions (>1%) were pneumonia, sepsis, dyspnea, pleural effusion, pulmonary embolism, pyrexia and respiratory tract infection.

TECENTRIQ was discontinued due to adverse reactions in 8% of patients. The most common adverse reactions leading to TECENTRIQ discontinuation were fatigue, infections and dyspnea. Adverse reactions leading to interruption of TECENTRIQ occurred in 25% of patients; the most common (>1%) were pneumonia, liver function test abnormality, dyspnea, fatigue, pyrexia, and back pain.

Tables 12 and 13 summarize adverse reactions and laboratory abnormalities, respectively, in OAK.

Table 12: Adverse Reactions Occurring in ≥10% of Patients with NSCLC Receiving TECENTRIQ in OAK

Adverse ReactionTECENTRIQ
N = 609
Docetaxel
N = 578
All Grades
(%)
Grades 3-4
(%)
All Grades
(%)
Grades 3-4
(%)
General
Fatigue/Asthenia1444536
Pyrexia18<113<1
Respiratory
Cough226<121<1
Dyspnea222.8212.6
Metabolism and Nutrition
Decreased appetite23<1241.6
Musculoskeletal
Myalgia/Pain3201.320<1
Arthralgia120.5100.2
Gastrointestinal
Nausea18<123<1
Constipation18<114<1
Diarrhea16<1242
Skin
Rash412<1100
Graded per NCI CTCAE v4.0
1 Includes fatigue and asthenia
2 Includes cough and exertional cough
3 Includes musculoskeletal pain, musculoskeletal stiffness, musculoskeletal chest pain, myalgia
4 Includes rash, erythematous rash, generalized rash, maculopapular rash, papular rash, pruritic rash, pustular rash, pemphigoid

Table 13: Laboratory Abnormalities Worsening From Baseline Occurring in ≥20% of Patients with NSCLC Receiving TECENTRIQ in OAK

Laboratory AbnormalityTECENTRIQDocetaxel
All Grades
(%)
Grades 3-4
(%)
All Grades
(%)
Grades 3-4
(%)
Hematology
Anemia673827
Lymphocytopenia49146021
Chemistry
Hypoalbuminemia484503
Hyponatremia427316
Increased Alkaline Phosphatase392251
Increased AST313160.5
Increased ALT273140.5
Hypophosphatemia275234
Hypomagnesemia261211
Increased Creatinine232161
Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: TECENTRIQ (range: 546−585) and docetaxel (range: 532−560). Graded according to NCI CTCAE version 4.0

Metastatic Triple Negative Breast Cancer (TNBC)

The safety of TECENTRIQ in combination with paclitaxel protein-bound was evaluated in IMpassion130, a multicenter, international, randomized, double-blinded placebo-controlled trial in patients with locally advanced or metastatic TNBC who have not received prior chemotherapy for metastatic disease [see Clinical Studies]. Patients received TECENTRIQ 840 mg (n=452) or placebo (n=438) intravenously followed by paclitaxel protein-bound (100 mg/m2) intravenously. For each 28 day cycle, TECENTRIQ was administered on days 1 and 15 and paclitaxel protein-bound was administered on days 1, 8, and 15 until disease progression or unacceptable toxicity. In the safety-evaluable population, the median duration of exposure to TECENTRIQ was 5.5 months (range: 0-32 months) and paclitaxel protein-bound was 5.1 months (range: 0-31.5 months) in the TECENTRIQ and paclitaxel protein-bound arm. The median duration of exposure to placebo was 5.1 months (range: 0-25.1 months) and paclitaxel protein-bound was 5.0 months (range: 0-23.7 months) in the placebo and paclitaxel protein-bound arm.

Fatal adverse reactions occurred in 1.3%) of patients in the TECENTRIQ and paclitaxel protein-bound arm; these included septic shock, mucosal inflammation, auto-immune hepatitis, aspiration, pneumonia, pulmonary embolism.

Serious adverse reactions occurred in 23% of patients. The most frequent serious adverse reactions were pneumonia (2%), urinary tract infection (1%), dyspnea (1%), and pyrexia (1%).

Adverse reactions leading to discontinuation of TECENTRIQ occurred in 6% (29/452) of patients in the TECENTRIQ and paclitaxel protein-bound arm. The most common adverse reaction leading to TECENTRIQ discontinuation was peripheral neuropathy (<1%).

Adverse reactions leading to interruption of TECENTRIQ occurred in 31% of patients; the most common (≥ 2%) were neutropenia, neutrophil count decreased, hyperthyroidism, and pyrexia.

Immune-related adverse reactions requiring systemic corticosteroid therapy occurred in 13% (59/452) of patients in the TECENTRIQ and paclitaxel protein-bound arm.

Tables 14 and 15 summarize adverse reactions and selected laboratory abnormalities worsening from baseline in the TECENTRIQ treated patients.

Table 14: Adverse Reactions Occurring in ≥10% of Patients with TNBC in IMpassion130

Adverse ReactionTECENTRIQ with Paclitaxel Protein-Bound
N = 452
Placebo with Paclitaxel Protein-Bound
N = 438
All Grades
(%)
Grades 3–4
(%)
All Grades
(%)
Grades 3–4
(%)
Skin and Subcutaneous Tissue
Alopecia56<158<1
Rash17<116<1
Pruritus140100
Nervous System
Peripheral neuropathies1479445
Headache23<122<1
Dysgeusia140140
Dizziness140110
General
Fatigue474453.4
Pyrexia19<1110
Peripheral Edema15<1161.4
Asthenia12<111<1
Gastrointestinal
Nausea461.1381.8
Diarrhea331.3342.1
Constipation25<125<1
Vomiting20<1171.1
Abdominal pain10<112<1
Respiratory, Thoracic, and Mediastinal
Cough250190
Dyspnea16<115<1
Metabolism and Nutrition
Decreased Appetite20<118<1
Musculoskeletal and Connective Tissue
Arthralgia18<116<1
Back pain151.313<1
Myalgia14<115<1
Pain in extremity11<110<1
Endocrine
Hypothyroidism1403.40
Infections
Urinary tract infection12<111<1
Upper respiratory tract infection111.190
Nasopharyngitis11080
Graded per NCI CTCAE v4.0
1 Includes peripheral neuropathy, peripheral sensory neuropathy, paresthesia, and polyneuropathy

Table 15: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients with TNBC in IMpassion130

Laboratory AbnormalityTECENTRIQ with Paclitaxel Protein-BoundPlacebo in combination with Paclitaxel Protein-Bound
All Grades
(%)
Grades 3–4
(%)
All Grades
(%)
Grades 3–4
(%)
Hematology
Decreased Hemoglobin793.8733
Decreased Leukocytes7614719
Decreased Neutrophils58135413
Decreased Lymphocytes5413478
Increased Prothrombin INR25<125<1
Chemistry
Increased ALT436342.7
Increased AST424.9343.4
Decreased Calcium281.126<1
Decreased Sodium274.2252.7
Decreased Albumin27<125<1
Increased Alkaline Phosphatase253.3222.7
Decreased Phosphate223.6193.7
Increased Creatinine21<116<1
Each test incidence is based on the number of patients who had at least one on-study laboratory measurement available: TECENTRIQ with paclitaxel protein-bound (range: 316-452); placebo with paclitaxel protein-bound (range: 299-438). Graded per NCI CTCAE v4.0, except for increased creatinine which only includes patients with creatinine increase based on upper limit of normal definition for grade 1 events (NCI CTCAE v5.0).

Small Cell Lung Cancer (SCLC)

The safety of TECENTRIQ with carboplatin and etoposide was evaluated in IMpower133, a randomized, multicenter, double-blind, placebo-controlled trial in which 198 patients with ESSCLC received TECENTRIQ 1200 mg and carboplatin AUC 5 mg/mL/min on Day 1 and etoposide 100 mg/m2 intravenously on Days 1, 2 and 3 of each 21-day cycle for a maximum of 4 cycles, followed by TECENTRIQ 1200 mg every 3 weeks until disease progression or unacceptable toxicity [see Clinical Studies]. Among 198 patients receiving TECENTRIQ, 32% were exposed for 6 months or longer and 12% were exposed for 12 months or longer.

Fatal adverse reactions occurred in 2% of patients receiving TECENTRIQ. These included pneumonia, respiratory failure, neutropenia, and death (1 patient each).

Serious adverse reactions occurred in 37% of patients receiving TECENTRIQ. Serious adverse reactions in >2% were pneumonia (4.5%), neutropenia (3.5%), febrile neutropenia (2.5%), and thrombocytopenia (2.5%).

TECENTRIQ was discontinued due to adverse reactions in 11% of patients. The most frequent adverse reaction requiring permanent discontinuation in >2% of patients was infusion-related reactions (2.5%).

Adverse reactions leading to interruption of TECENTRIQ occurred in 59% of patients; the most common (>1%) were neutropenia (22%), anemia (9%), leukopenia (7%), thrombocytopenia (5%), fatigue (4.0%), infusion-related reaction (3.5%), pneumonia (2.0%), febrile neutropenia (1.5%), increased ALT (1.5%), and nausea (1.5%).

Tables 16 and 17 summarize adverse reactions and laboratory abnormalities, respectively, in patients who received TECENTRIQ with carboplatin and etoposide in IMpower133.

Table 16: Adverse Reactions Occurring in ≥20% of Patients with SCLC Receiving TECENTRIQ in IMpower133

Adverse ReactionTECENTRIQ with Carboplatin and Etoposide
N = 198
Placebo with Carboplatin and Etoposide
N = 196
All Grades
(%)
Grades 3–4
(%)
All Grades
(%)
Grades 3–4
(%)
General
Fatigue/asthenia395333
Gastrointestinal
Nausea381331
Constipation261301
Vomiting202173
Skin and Subcutaneous Tissue
Alopecia370350
Metabolism and Nutrition
Decreased appetite271180
Graded per NCI CTCAE v4.0

Table 17: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients with SCLC Receiving TECENTRIQ in IMpower133

Laboratory AbnormalityTECENTRIQ with Carboplatin and EtoposidePlacebo with Carboplatin and Etoposide
All Grades
(%)
Grades 3–4
(%)
All Grades
(%)
Grades 3–4
(%)
Hematology
Anemia94179319
Neutropenia73457648
Thrombocytopenia58205317
Lymphopenia46143811
Chemistry
Hyperglycemia6710658
Increased Alkaline Phosphatase381352
Hyponatremia34153311
Hypoalbuminemia321300
Decreased TSH228NA115NA1
Hypomagnesemia315356
Hypocalcemia263285
Increased ALT263311
Increased AST221212
Increased Blood Creatinine224151
Hyperphosphatemia21NA123NA1
Increased TSH221NA17NA1
Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: TECENTRIQ (range: 181-193); Placebo (range: 181-196). Graded per NCI CTCAE v4.0
1 NA= Not applicable.
2 TSH = thyroid-stimulating hormone. NCI CTCAE v4.0 does not include these laboratories.

Hepatocellular Carcinoma (HCC)

The safety of TECENTRIQ in combination with bevacizumab was evaluated in IMbrave150, a multicenter, international, randomized, open-label trial in patients with locally advanced or metastatic or unresectable hepatocelullar carcinoma who have not received prior systemic treatment [see Clinical Studies]. Patients received 1,200 mg of TECENTRIQ intravenously followed by 15 mg/kg bevacizumab (n=329) every 3 weeks, or 400 mg of sorafenib (n=156) given orally twice daily, until disease progression or unacceptable toxicity. The median duration of exposure to TECENTRIQ was 7.4 months (range: 0-16 months) and to bevacizumab was 6.9 months (range: 0-16 months).

Fatal adverse reactions occurred in 4.6% of patients in the TECENTRIQ and bevacizumab arm. The most common adverse reactions leading to death were gastrointestinal and esophageal varices hemorrhage (1.2%) and infections (1.2%).

Serious adverse reactions occurred in 38% of patients in the TECENTRIQ and bevacizumab arm. The most frequent serious adverse reactions (≥ 2%) were gastrointestinal hemorrhage (7%), infections (6%), and pyrexia (2.1%).

Adverse reactions leading to discontinuation of TECENTRIQ occurred in 9% of patients in the TECENTRIQ and bevacizumab arm. The most common adverse reactions leading to TECENTRIQ discontinuation were hemorrhages (1.2%), including gastrointestinal, subarachnoid, and pulmonary hemorrhages; increased transaminases or bilirubin (1.2%); infusion-related reaction/cytokine release syndrome (0.9%); and autoimmune hepatitis (0.6%).

Adverse reactions leading to interruption of TECENTRIQ occurred in 41% of patients in the TECENTRIQ and bevacizumab arm; the most common (≥ 2%) were liver function laboratory abnormalities including increased transaminases, bilirubin, or alkaline phosphatate (8%); infections (6%); gastrointestinal hemorrhages (3.6%); thrombocytopenia/decreased platelet count (3.6%); hyperthyroidism (2.7%); and pyrexia (2.1%).

Immune-related adverse reactions requiring systemic corticosteroid therapy occurred in 12% of patients in the TECENTRIQ and bevacizumab arm.

Tables 18 and 19 summarize adverse reactions and laboratory abnormalities, respectively, in patients who received TECENTRIQ and bevacizumab in IMbrave150.

Table 18: Adverse Reactions Occurring in ≥10% of Patients with HCC Receiving TECENTRIQ in IMbrave150

Adverse ReactionTECENTRIQ in combination with bevacizumab
(n = 329)
Sorafenib
(n=156)
All Grades1
(%)
Grades 3–41
(%)
All Grades1
(%)
Grades 3–41
(%)
Vascular Disorders
Hypertension30152412
General Disorders and Administration Site Conditions
Fatigue/asthenia1262326
Pyrexia180100
Renal and Urinary Disorders
Proteinuria20370.6
Investigations
Weight Decreased110100
Skin and Subcutaneous Tissue Disorders
Pruritus190100
Rash120172.6
Gastrointestinal Disorders
Diarrhea191.8495
Constipation130140
Abdominal Pain120170
Nausea120160
Vomiting10080
Metabolism and Nutrition Disorders
Decreased Appetite181.2243.8
Respiratory, Thoracic and Mediastinal Disorders
Cough120100
Epistaxis1004.50
Injury, Poisoning and Procedural Complications
Infusion Related Reaction112.400
1 Includes fatigue and asthenia
2 Graded per NCI CTCAE v4.0

Table 19: Laboratory Abnormalities Worsening from Baseline Occurring in ≥20% of Patients with HCC Receiving TECENTRIQ in IMbrave150

Laboratory AbnormalityTECENTRIQ in combination with bevacizumab
(n=329)
Sorafenib
(n=156)
All Grades1
(%)
Grades 3–41
(%)
All Grades1
(%)
Grades 3–41
(%)
Chemistry
Increased AST86169016
Increased Alkaline Phosphatase704764.6
Increased ALT628704.6
Decreased Albumin601.5540.7
Decreased Sodium5413499
Increased Glucose489434.6
Decreased Calcium300.3351.3
Decreased Phosphorus264.75816
Increased Potassium231.9162
Hypomagnesemia220220
Hematology
Decreased Platelet687634.6
Decreased Lymphocytes62135811
Decreased Hemoglobin583.1623.9
Increased Bilirubin5785914
Decreased Leukocyte323.4291.3
Decreased Neutrophil232.3161.1
Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: TECENTRIQ plus bevacizumab (222-323) and sorafenib (90-153)
NA = Not applicable.
1 Graded per NCI CTCAE v4.0

Melanoma

The safety of TECENTRIQ, administered with cobimetinib and vemurafenib was evaluated in IMspire150, a double-blind, randomized (1:1), placebo-controlled study conducted in patients with previously untreated BRAF V600 mutation-positive metastatic or unresectable melanoma [see Clinical Studies]. Patients received TECENTRIQ with cobimetinib and vemurafenib (N=230) or placebo with cobimetinib and vemurafenib (n=281).

Among the 230 patients who received TECENTRIQ administered with cobimetinib and vemurafenib, the median duration of exposure to TECENTRIQ was 9.2 months (range: 0-30 months) to cobimetinib was 10.0 months (range: 1-31 months) and to vemurafenib was 9.8 months (range: 1-31 months).

Fatal adverse reactions occurred in 3% of patients in the TECENTRIQ plus cobimetinib and vemurafenib arm. Adverse reactions leading to death were hepatic failure, fulminant hepatitis, sepsis, septic shock, pneumonia, and cardiac arrest.

Serious adverse reactions occurred in 45% of patients in the TECENTRIQ plus cobimetinib and vemurafenib arm. The most frequent (≥ 2%) serious adverse reactions were hepatotoxicity (7%), pyrexia (6%), pneumonia (4.3%), malignant neoplasms (2.2%), and acute kidney injury (2.2%).

Adverse reactions leading to discontinuation of TECENTRIQ occurred in 21% of patients in the TECENTRIQ plus cobimetinib and vemurafenib arm. The most frequent (≥ 2%) adverse reactions leading to TECENTRIQ discontinuation were increased ALT (2.2%) and pneumonitis (2.6%).

Adverse reactions leading to interruption of TECENTRIQ occurred in 68% of patients in the TECENTRIQ plus cobimetinib and vemurafenib arm. The most frequent (≥ 2%) adverse reactions leading to TECENTRIQ interruption were pyrexia (14%), increased ALT (13%), hyperthyroidism (10%), increased AST (10%), increased lipase (9%), increased amylase (7%), pneumonitis (5%), increased CPK (4.3%), diarrhea (3.5%), pneumonia (3.5%), asthenia (3%), rash (3%), influenza (3%), arthralgia (2.6%), fatigue (2.2%), dyspnea (2.2%), cough (2.2%), peripheral edema (2.2%), uveitis (2.2%), bronchitis (2.2%), hypothyroidism (2.2%), and respiratory tract infection (2.2%).

Tables 20 and 21 summarizes the incidence of adverse reactions and laboratory abnormalities in Study IMspire150.

Table 20: Adverse Reactions Occurring in ≥10% of Patients on the TECENTRIQ plus Cobimetinib and Vemurafenib Arm or the Placebo plus Cobimetinib and Vemurafenib Arm and at a Higher Incidence (Between Arm Difference of ≥ 5% All Grades or ≥ 2% Grades 3-4 TECENTRIQ in IMspire150)

Adverse ReactionTECENTRIQ in combination with Cobimetinib and Vemurafenib
(n=230)
Placebo with Cobimetinib and Vemurafenib
(n=281)
All Grades
(%)
Grade 3–4
(%)
All Grades
(%)
Grade 3–4
(%)
Skin and Subcutaneous Tissue Disorders
Rash 175277223
Pruritus26<117<1
Photosensitivity reaction21<1253.2
General Disorders and Administration Site Conditions
Fatigue 2513451.8
Pyrexia 3491.7352.1
Edema 426<1210
Gastrointestinal Disorders
Hepatotoxicity 550213613
Nausea30<1322.5
Stomatitis 6231.315<1
Musculoskeletal and Connective Tissue Disorders
Musculoskeletal pain 7624.3483.2
Endocrine Disorders
Hypothyroidism 8220100
Hyperthyroidism18<180
Injury, Poisoning and Procedural Complications
Infusion related reaction 9102.68<1
Respiratory, Thoracic and Mediastinal Disorders
Pneumonitis 10121.36<1
Vascular Disorders
Hypertension 111710187
1 Includes rash, rash maculo-papular, dermatitis acneiform, rash macular, rash erythematous, eczema, skin exfoliation, rash papular, rash pustular, palmar-plantar erythrodysaesthesia syndrome, dermatitis, dermatitis contact, erythema multiforme, rash pruritic, drug eruption, nodular rash, dermatitis allergic, exfoliative rash, dermatitis exfoliative generalised and rash morbilliform
2 Includes fatigue, asthenia and malaise
3 Includes pyrexia and hyperpyrexia
4 Includes edema peripheral, lymphoedema, oedema, face oedema, eyelid oedema, periorbital oedema, lip oedema and generalised oedema
5 Includes alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, transaminases increased, hepatitis, hepatic enzyme increased, hepatotoxicity, hypertransaminasaemia, bilirubin conjugated increased, hepatocellular injury, hyperbilirubinaemia, liver function test increased, hepatic failure, hepatitis fulminant and liver function test abnormal
6 Inlcudes stomatitis, mucosal inflammation, aphthous ulcer, mouth ulceration, cheilitis and glossitis
7 Includes arthralgia, myalgia, pain in extremity, back pain, musculoskeletal pain, arthritis, neck pain, musculoskeletal chest pain, musculoskeletal stiffness, bone pain, spinal pain, immune-mediated arthritis, joint stiffness and non-cardiac chest pain
8 Includes hypothyroidism and blood thyroid stimulating hormone increased
9 Includes infusion related reaction and hypersensitivity
10 Includes pneumonitis and interstitial lung disease
11 Includes hypertension, blood pressure increased, hypertensive crisis

Clinically important adverse reactions in < 10% of patients who received TECENTRIQ plus cobimetinib and vemurafenib were:

Cardiac Disorders: Arrhythmias, ejection fraction decreased, electrocardiogram QT prolonged

Eye Disorders: Uveitis

Gastrointestinal disorders: Pancreatitis

Infections and infestations: Pneumonia, urinary tract infection

Metabolism and nutrition disorders: Hyperglycemia

Nervous system Disorders: Dizziness, dysgeusia, syncope

Respiratory, thoracic and mediastinal disorders: Dyspnea, oropharyngeal pain

Skin and Subcutaneous Tissue Disorders: Vitiligo

Table 21: Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% of Patients Receiving TECENTRIQ plus Cobimetinib and Vemurafenib Arm or the Placebo plus Cobimetinib and Vemurafenib Arm and at a Higher Incidence (Between Arm Difference of ≥ 5% All Grades or ≥ 2% Grades 3-4) in IMspire150

Laboratory AbnormalityTECENTRIQ in combination with Cobimetinib and Vemurafenib
(n=230)
Placebo with Cobimetinib and Vemurafenib
(n=281)
All Grades
(%)
Grade 3–4
(%)
All Grades
(%)
Grade 3–4
(%)
Hematology
Decreased Lymphocytes80247217
Decreased Hemoglobin772.6722.2
Decreased Platelet341.3240.4
Decreased Neutrophils262.2191.5
Chemistry
Increased Creatine Kinase88228118
Increased AST8013686
Increased ALT79186212
Increased Triacylglycerol Lipase75466235
Increased Alkaline Phosphatase736632.9
Decreased Phosphorus67226414
Increased Amylase51134513
Increased Blood Urea Nitrogen47NA137NA1
Decreased Albumin430.9341.5
Increased Bilirubin423.1330.7
Decreased Calcium411.3280
Decreased Sodium405347
Decreased Thyroid-Stimulating Hormone38NA123NA1
Increased Thyroid-Stimulating Hormone 237NA133NA1
Decreased Potassium365224.3
Increased Triiodothyronine33NA118NA1
Increased Free Thyroxine32NA121NA1
Decreased Total Triiodothyronine32NA18NA1
Increased Potassium291.3191.4
Decreased Triiodothyronine27NA121NA1
Increased Sodium200130.4
Graded per NCI CTCAE v4.0.
Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: TECENTRIQ plus cobimetinib and vemurafenib (28-277), placebo plus cobimetinib and vemurafenib arm (25-230).
1 NA= Not applicable. NCI CTCAE v4.0 does not include these laboratories.
2 Increased Thyroid Stimulating Hormone has a difference <5% (All Grades) between arms and is included for clinical completeness.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to atezolizumab in the studies described above with the incidence of antibodies in other studies or to other products may be misleading.

Among 565 patients with NSCLC in OAK, 30% tested positive for treatment-emergent anti-drug antibodies (ADA) at one or more post-dose time points. The median onset time to ADA formation was 3 weeks. The ability of these binding ADA to neutralize atezolizumab is unknown. Patients who tested positive for treatment-emergent ADA also had decreased systemic atezolizumab exposure [see CLINICAL PHARMACOLOGY]. Exploratory analyses showed that the subset of patients who were ADA positive by week 4 (21%; 118/560) appeared to have less efficacy (effect on overall survival) as compared to patients who tested negative for treatment-emergent ADA by week 4 [see Clinical Studies]. The presence of ADA did not have a clinically significant effect on the incidence or severity of adverse reactions.

Among 275 patients with urothelial carcinoma in IMvigor210 (Cohort 2), 42% tested positive for treatment-emergent ADA at one or more post-dose time points. Among 111 patients in IMvigor210 (Cohort 1), 48% tested positive for treatment-emergent ADA at one or more post-dose time points. Patients who tested positive for treatment-emergent ADA also had decreased systemic atezolizumab exposures. The presence of ADA did not have a clinically significant effect on the incidence or severity of adverse reactions.

Among 364 ADA-evaluable patients with NSCLC who received TECENTRIQ with bevacizumab, paclitaxel and carboplatin in IMpower150, 36% (n=132) tested positive for treatment-emergent ADA at one or more post-dose time points and 83% of these 132 patients tested ADA positive prior to receiving the second dose of atezolizumab. The ability of these binding ADA to neutralize atezolizumab is unknown. Patients who tested positive for treatment-emergent ADA had lower systemic atezolizumab exposure as compared to patients who were ADA negative [see CLINICAL PHARMACOLOGY]. The presence of ADA did not increase the incidence or severity of adverse reactions [see Clinical Studies].

Among 434 patients with TNBC in IMpassion130, 13% tested positive for treatment-emergent ADA at one or more post-dose time points. Among 178 patients in PD-L1 positive subgroup with TNBC in IMpassion130, 12% tested positive for treatment-emergent ADA at one or more post-dose time points. Patients who tested positive for treatment-emergent ADA had decreased systemic atezolizumab exposure [see CLINICAL PHARMACOLOGY]. There are insufficient numbers of patients in the PD-L1 positive subgroup with ADA to determine whether ADA alters the efficacy of atezolizumab. The presence of ADA did not have a clinically significant effect on the incidence or severity of adverse reactions.

Among 315 ADA-evaluable patients with HCC who received TECENTRIQ and bevacizumab in IMbrave150, 28% (n=88) tested positive for treatment-emergent ADA at one or more post-dose time points and 66% (58/88) of these 88 patients tested ADA-positive prior to receiving the third dose of TECENTRIQ. The ability of these binding ADA to neutralize atezolizumab is unknown. Patients who tested positive for treatment-emergent ADA had lower systemic atezolizumab exposure as compared to patients who were ADA-negative [see CLINICAL PHARMACOLOGY]. Exploratory analyses showed that the subset of patients who were ADA-positive by week 6 (20%; 58/288) appeared to have less efficacy (effect on overall survival) as compared to patients who tested negative for treatment-emergent ADA by week 6; [see Clinical Studies (14.5)]. The presence of ADA did not have a clinically significant effect on the incidence or severity of adverse reactions.

Among 218 ADA-evaluable patients with melanoma who received TECENTRIQ in combination with cobimetinib and vemurafenib in IMspire150, 13% (n=29) tested positive for treatment-emergent ADA at one or more post-dose time points. Patients who tested positive for treatment-emergent ADA had decreased systemic atezolizumab exposure [see CLINICAL PHARMACOLOGY]. There are insufficient numbers of patients with positive ADA to determine whether ADA alters the efficacy or incidence or severity of adverse reactions.

Read the entire FDA prescribing information for Tecentriq (Atezolizumab Injection)

Related Resources for Tecentriq

© Tecentriq Patient Information is supplied by Cerner Multum, Inc. and Tecentriq Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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