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Tecentriq特善奇

Tecentriq Adverse Reactions

atezolizumab

Manufacturer:

Roche

Distributor:

DKSH
/
Agencia Lei Va Hong
Full Prescribing Info
Adverse Reactions
Summary of the safety profile: 840 mg/14 mL: The safety of atezolizumab as monotherapy is based on pooled data in 3,178 patients across multiple tumour types. The most common adverse reactions (> 10%) were fatigue (35.9%), decreased appetite (25.5%), nausea (23.5%), cough (20.8%), dyspnoea (20.5%), pyrexia (20.1%), diarrhoea (19.7%), rash (19.5%), back pain (15.3%), vomiting (15.0%), asthenia (14.5%), arthralgia (13.9%), musculoskeletal pain (13.0%), pruritus (12.6%) and urinary tract infection (11.6%).
The safety of atezolizumab given in combination with other medicinal products, has been evaluated in 2,759 patients across multiple tumour types. The most common adverse reactions (≥ 20%) were nausea (37.4%), fatigue (36.4%), neutropenia (33.7%), anaemia (33.2%), diarrhoea (29.5%), rash (28.5%), constipation (27.0%), peripheral neuropathy (26.8%), decreased appetite (24.6%), thrombocytopenia (21.2%) and cough (20.1%).
Further details on serious adverse reactions are provided in Precautions.
1,200 mg/20 mL: The safety of atezolizumab as monotherapy is based on pooled data in 3,568 patients across multiple tumour types. The most common adverse reactions (> 10%) were fatigue (34.5%), decreased appetite (24.0%), nausea (22.4%), pyrexia (20.1%), diarrhoea (19.9%), cough (19.8%), rash (19.8%), dyspnoea (19.0%), musculoskeletal pain (14.7%), back pain (14.4%), vomiting (14.1%), pruritus (14.0%), asthenia (13.9%), arthralgia (13.6%), urinary tract infection (13.1%) and headache (10.9%).
The safety of atezolizumab given in combination with other medicinal products, has been evaluated in 4,371 patients across multiple tumour types. The most common adverse reactions (≥ 20%) were anaemia (36.8 %), neutropenia (35.8%), nausea (34.4%), fatigue (33.0%), thrombocytopenia (27.7 %), rash (27.2%), diarrhoea (27.1%), alopecia (26.4%), constipation (25.7%), decreased appetite (25.0%) and peripheral neuropathy (23.0%).
Further details on serious adverse reactions are provided in Precautions.
Tabulated list of adverse reactions: The Adverse Drug Reactions (ADRs) are listed by MedDRA system organ class (SOC) and categories of frequency in Tables 18, 19a and 19b for atezolizumab given as monotherapy or as combination therapy. Adverse reactions known to occur with atezolizumab or chemotherapies given alone may occur during treatment with these medicinal products in combination, even if these reactions were not reported in clinical trials with combination therapy. The following categories of frequency have been used: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
840 mg/14 mL: See Table 18.

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1,200 mg/20 mL: See Tables 19a and 19b.

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Description of selected adverse reactions: The following data reflect information for significant adverse reactions for atezolizumab as monotherapy in clinical studies (see Pharmacology: Pharmacodynamics under Actions). Details for the significant adverse reactions for atezolizumab when given in combination are presented if clinically relevant differences were noted in comparison to atezolizumab monotherapy. The management guidelines for these adverse reactions are described in Dosage & Administration and Precautions.
Immune-related pneumonitis: 840 mg/14 mL: Pneumonitis occurred in 2.7% (87/3,178) of patients who received atezolizumab monotherapy. Of the 87 patients, one experienced a fatal event. The median time to onset was 3.4 months (range 3 days to 24.8 months). The median duration was 1.4 months (range 0 day to 21.2+ months; + denotes a censored value). Pneumonitis led to discontinuation of atezolizumab in 12 (0.4%) patients. Pneumonitis requiring the use of corticosteroids occurred in 1.6% (51/3,178) of patients receiving atezolizumab monotherapy.
1,200 mg/20 mL: Pneumonitis occurred in 2.8% (99/3,568) of patients who received atezolizumab monotherapy. Of the 99 patients, one experienced a fatal event. The median time to onset was 4.0 months (range 3 days to 24.8 months). The median duration was 1.6 months (range 0 day to 21.7+ months; + denotes a censored value). Pneumonitis led to discontinuation of atezolizumab in 15 (0.4%) patients. Pneumonitis requiring the use of corticosteroids occurred in 1.5% (53/3,568) of patients receiving atezolizumab monotherapy.
Immune-related hepatitis: 840 mg/14 mL: Hepatitis occurred in 2.0% (62/3,178) of patients who received atezolizumab monotherapy. Of the 62 patients, two experienced a fatal event. The median time to onset was 1.5 months (range 6 days to 18.8 months). The median duration was 2.1 months (range 0 day to 22.0+ months; + denotes a censored value). Hepatitis led to discontinuation of atezolizumab in 6 (< 0.2%) patients. Hepatitis requiring the use of corticosteroids occurred in 0.6% (18/3,178) of patients receiving atezolizumab monotherapy.
1,200 mg/20 mL: Hepatitis occurred in 1.8% (66/3,568) of patients who received atezolizumab monotherapy. Of the 66 patients, two experienced a fatal event. The median time to onset was 1.5 months (range 6 days to 18.8 months). The median duration was 2.1 months (range 0 day to 22.0+ months; + denotes a censored value). Hepatitis led to discontinuation of atezolizumab in 9 (0.3%) patients. Hepatitis requiring the use of corticosteroids occurred in 0.5% (19/3,568) of patients receiving atezolizumab monotherapy.
Immune-related colitis: 840 mg/14 mL: Colitis occurred in 1.1% (34/3,178) of patients who received atezolizumab monotherapy. The median time to onset was 4.7 months (range 15 days to 17.2 months). The median duration was 1.2 months (range 3 days to 17.8+ months; + denotes a censored value). Colitis led to discontinuation of atezolizumab in 8 (0.3%) patients. Colitis requiring the use of corticosteroids occurred in 0.6% (19/3,178) of patients receiving atezolizumab monotherapy.
1,200 mg/20 mL: Colitis occurred in 1.2% (43/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 5.0 months (range 15 days to 17.2 months). The median duration was 1.2 months (range 3 days to 17.8+ months; + denotes a censored value). Colitis led to discontinuation of atezolizumab in 15 (0.4%) patients. Colitis requiring the use of corticosteroids occurred in 0.5% (19/3,568) of patients receiving atezolizumab monotherapy.
Immune-related endocrinopathies: Thyroid disorders: 840 mg/14 mL: Hypothyroidism occurred in 5.2% (164/3,178) of patients who received atezolizumab monotherapy. The median time to onset was 4.9 months (range: 0 day to 31.3 months). Hyperthyroidism occurred in 0.9% (30/3,178) of patients who received atezolizumab monotherapy. The median time to onset was 2.1 months (range 21 days to 15.7 months).
1,200 mg/20 mL: Hypothyroidism occurred in 6.0% (214/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 4.4 months (range: 0 day to 31.3 months). Hyperthyroidism occurred in 1.3% (47/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 2.1 months (range 21 days to 15.7 months).
Adrenal insufficiency: 840 mg/14 mL: Adrenal insufficiency occurred in 0.4% (12/3,178) of patients who received atezolizumab monotherapy. The median time to onset was 5.5 months (range: 3 days to 19 months). The median duration was 16.8 months (range: 0 day to 16.8 months). Adrenal insufficiency led to discontinuation of atezolizumab in 1 (<0.1%) patient. Adrenal insufficiency requiring the use of corticosteroids occurred in 0.3% (9/3,178) of patients receiving atezolizumab monotherapy.
1,200 mg/20 mL: Adrenal insufficiency occurred in 0.4% (13/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 5.7 months (range: 3 days to 19 months). The median duration was 16.8 months (range: 0 day to 20.9+ months; + denotes a censored value). Adrenal insufficiency led to discontinuation of atezolizumab in 1 (<0.1%) patient. Adrenal insufficiency requiring the use of corticosteroids occurred in 0.3% (10/3,568) of patients receiving atezolizumab monotherapy.
Hypophysitis: 840 mg/14 mL: Hypophysitis occurred in < 0.1% (2/3,178) of patients who received atezolizumab monotherapy. The median time to onset 7.2 months (range: 24 days to 13.7 months). One patient required the use of corticosteroids and treatment with atezolizumab was discontinued.
Hypophysitis occurred in 0.8% (3/393) of patients who received atezolizumab with bevacizumab, paclitaxel, and carboplatin. The median time to onset was 7.7 months (range: 5.0 to 8.8 months). Two patients required the use of corticosteroids.
Hypophysitis occurred in 0.4% (2/473) of patients who received atezolizumab in combination with nab-paclitaxel and carboplatin. The median time to onset was 5.2 months (range: 5.1 to 5.3 months). Both patients required the use of corticosteroids.
1,200 mg/20 mL: Hypophysitis occurred in < 0.1% (3/3,568) of patients who received atezolizumab monotherapy. The median time to onset 5.3 months (range: 24 days to 13.7 months). Two (<0.1%) patients required the use of corticosteroids and treatment with atezolizumab was discontinued in 1 (<0.1%) patient. Hypophysitis occurred in 0.8% (3/393) of patients who received atezolizumab with bevacizumab, paclitaxel, and carboplatin. The median time to onset was 7.7 months (range: 5.0 to 8.8 months). Two patients required the use of corticosteroids.
Hypophysitis occurred in 0.4% (2/473) of patients who received atezolizumab in combination with nab-paclitaxel and carboplatin. The median time to onset was 5.2 months (range: 5.1 to 5.3 months). Both patients required the use of corticosteroids.
Diabetes mellitus: 840 mg/14 mL: Diabetes mellitus occurred in 0.3% (11/3,178) of patients who received atezolizumab monotherapy. The median time to onset was 3.6 months (range 3 days to 9.9 months). Diabetes mellitus led to the discontinuation of atezolizumab in < 0.1% (3/3,178) patients.
1,200 mg/20 mL: Diabetes mellitus occurred in 0.3% (11/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 4.2 months (range 3 days to 9.9 months). Diabetes mellitus requiring the use of corticosteroids occurred in < 0.1% (2/3,568) of patients receiving atezolizumab monotherapy. Diabetes mellitus led to the discontinuation of atezolizumab in < 0.1% (3/3,568) patients.
Diabetes mellitus occurred in 2.0% (10/493) of HCC patients who received atezolizumab in combination with bevacizumab. The median time to onset was 4.4 months (range: 1.2 months - 8.3 months). No events of diabetes mellitus led to atezolizumab withdrawal.
Immune-related meningoencephalitis: 840 mg/14 mL: Meningoencephalitis occurred in 0.4% (13/3,178) of patients who received atezolizumab monotherapy. The median time to onset was 15 days (range: 0 day to 12.5 months). The median duration was 26 days (range 6 days to 14.5+ months; + denotes a censored value).
Meningoencephalitis requiring the use of corticosteroids occurred in 0.2% (6/3,178) of patients receiving atezolizumab and four patients discontinued atezolizumab.
1,200 mg/20 mL: Meningoencephalitis occurred in 0.4% (14/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 15 days (range: 0 day to 12.5 months). The median duration was 21 days (range 6 days to 14.5+ months; + denotes a censored value).
Meningoencephalitis requiring the use of corticosteroids occurred in 0.2% (6/3,568) of patients receiving atezolizumab and four patients discontinued atezolizumab.
Immune-related neuropathies: 840 mg/14 mL: Guillain-Barré syndrome and demyelinating polyneuropathy occurred in 0.2% (5/3,178) of patients who received atezolizumab monotherapy. The median time to onset was 7 months (range: 18 days to 8.1 months). The median duration was 8.0 months (range 18 days to 8.3+ months; + denotes a censored value). Guillain-Barré syndrome led to discontinuation of atezolizumab in 1 patient (< 0.1%). Guillain-Barré syndrome requiring the use of corticosteroids occurred in < 0.1% (2/3,178) of patients receiving atezolizumab monotherapy.
1,200 mg/20 mL: Guillain-Barré syndrome and demyelinating polyneuropathy occurred in 0.1% (5/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 7 months (range: 18 days to 8.1 months). The median duration was 8.0 months (range 18 days to 8.3+ months; + denotes a censored value). Guillain-Barré syndrome led to discontinuation of atezolizumab in 1 patient (< 0.1%). Guillain-Barré syndrome requiring the use of corticosteroids occurred in < 0.1% (2/3,568) of patients receiving atezolizumab monotherapy.
Myasthenic syndrome: 840 mg/14 mL: Myasthenia gravis occurred in < 0.1% (1/3,178) of patients who received atezolizumab monotherapy. The time to onset was 1.2 months.
1,200 mg/20 mL: Myasthenia gravis occurred in < 0.1% (1/3,568) of patients who received atezolizumab monotherapy. The time to onset was 1.2 months.
Immune-related pancreatitis: 840 mg/14 mL: Pancreatitis, including amylase increased and lipase increased, occurred in 0.6% (18/3,178) of patients who received atezolizumab monotherapy. The median time to onset was 5.0 months (range: 9 days to 16.9 months). The median duration was 24 days (range 3 days to 12.0+ months; + denotes a censored value). Pancreatitis led to the discontinuation of atezolizumab in 3 (< 0.1%) patients. Pancreatitis requiring the use of corticosteroids occurred in 0.1% (4/3,178) of patients receiving atezolizumab monotherapy.
1,200 mg/20 mL: Pancreatitis, including amylase increased and lipase increased, occurred in 0.8% (27/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 4.3 months (range: 0 days to 16.9 months). The median duration was 27 days (range 3 days to 22.4+ months; + denotes a censored value). Pancreatitis led to the discontinuation of atezolizumab in 3 (< 0.1%) patients. Pancreatitis requiring the use of corticosteroids occurred in 0.1% (4/3,568) of patients receiving atezolizumab monotherapy.
Immune-related myocarditis: Myocarditis occurred in < 0.1% (2/8,000) of patients across all atezolizumab clinical trials in multiple tumour types and treatment combinations. The time to onset was 18 and 33 days. Both patients required corticosteroids and discontinued atezolizumab.
Immune-related nephritis:
840 mg/14 mL: Nephritis occurred in < 0.1% (3/3,178) of patients who received atezolizumab. The median time to onset was 13.1 months (range: 9.0 to 17.5 months). The median duration was 2.8 months (range 15 days to 9.5+ months; + denotes a censored value). Nephritis led to discontinuation of atezolizumab in 2 (<0.1%) patients. One patient required corticosteroids and discontinued atezolizumab.
1,200 mg/20 mL: Nephritis occurred in 0.2% (8/3,568) of patients who received atezolizumab. The median time to onset was 6.0 months (range: 2.0 to 17.5 months). Nephritis led to discontinuation of atezolizumab in 4/3,568 (0.1%) patients. Two (<0.1%) patients required corticosteroids.
Immune-related myositis: 840 mg/14 mL: Myositis occurred in 0.4% (12/3178) of patients who received atezolizumab monotherapy. The median time to onset was 5.4 months (range: 0.7 to 11.0 months). The median duration was 3.5 months (range 0.1 to 22.6+ months; + denotes a censored value). Myositis led to discontinuation of atezolizumab in 1 (<0.1%) patient. Seven (0.2%) patients required the use of corticosteroids.
1,200 mg/20 mL: Myositis occurred in 0.4% (15/3,568) of patients who received atezolizumab monotherapy. The median time to onset was 2.9 months (range: 0.4 to 11.0 months). The median duration was 3.8 months (range 3 days to 22.6+ months; + denotes a censored value). Myositis led to discontinuation of atezolizumab in 1 (<0.1%) patient. Seven (0.2%) patients required the use of corticosteroids.
Use of atezolizumab in combination with bevacizumab, paclitaxel and carboplatin: In the first-line NSCLC study (IMpower150), an overall higher frequency of adverse events was observed in the four-drug regimen of atezolizumab, bevacizumab, paclitaxel, and carboplatin compared to atezolizumab, paclitaxel and carboplatin, including Grade 3 and 4 events (63.6% compared to 57.5%), Grade 5 events (6.1% compared to 2.5%), adverse events of special interest to atezolizumab (52.4% compared to 48.0%), as well as adverse events leading to withdrawal of any study treatment (33.8% compared to 13.3%). Nausea, diarrhoea, stomatitis, fatigue, pyrexia, mucosal inflammation, decreased appetite, weight decreased, hypertension and proteinuria were reported higher (≥5% difference) in patients receiving atezolizumab in combination with bevacizumab, paclitaxel and carboplatin. Other clinically significant adverse events which were observed more frequently in the atezolizumab, bevacizumab, paclitaxel, and carboplatin arm were epistaxis, haemoptysis, cerebrovascular accident, including fatal events.
Immunogenicity: 840 mg/14 mL: Across multiple phase III studies, 13.1% to 36.4% of patients developed treatment-emergent anti-drug antibodies (ADAs). Overall, ADA status appeared to have no clinically relevant impact on safety. No data are available to allow conclusions to be drawn on possible effects of neutralising antibodies.
1,200 mg/20 mL: Across multiple phase III studies, 13.1 % to 36.4% of patients developed treatment-emergent anti-drug antibodies (ADAs).
Across pooled datasets for patients treated with atezolizumab monotherapy (N=2705) and with combination therapies (N= 2285), the following rates of adverse events (AEs) have been observed for the ADA-positive population compared to the ADA-negative population, respectively: Grade 3-4 AEs 49.1% vs. 44.3%, Serious Adverse Events (SAEs) 42.4% vs. 37.6%, AEs leading to treatment withdrawal 6.1% vs 6.7% (for monotherapy); Grade 3-4 AEs 63.9% vs. 60.9%, SAEs 43.9% vs. 35.6%, AEs leading to treatment withdrawal 22.8% vs 18.4% (for combination therapy). However, available data do not allow firm conclusions to be drawn on possible patterns of adverse drug reactions.
Elderly patients: No overall differences in safety were observed between patients ≥ 65 years of age and younger patients receiving atezolizumab monotherapy. In study IMpower150, age ≥ 65 was associated with an increased risk of developing adverse events in patients receiving atezolizumab in combination with bevacizumab, carboplatin and paclitaxel.
In studies IMpower150 and IMpower133, data for patients ≥75 years of age are too limited to draw conclusions on this population.
Paediatric population: 1,200 mg/20 mL: The safety of atezolizumab in children and adolescents has not been established. No new safety signals were observed in a clinical study with 69 paediatric patients (<18 years) and the safety profile was comparable to adults.
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