Summary of the safety profile Avelumab is associated with immune-mediated adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of avelumab (see “Description of selected adverse reactions” below).
5%). 6%). 4). Tabulated list of adverse reactions The safety of avelumab as monotherapy has been evaluated in 2 082 patients with solid tumours including metastatic MCC or locally advanced or metastatic UC receiving 10 mg/kg every 2 weeks of avelumab in clinical studies or reported from post-marketing use of avelumab (see Table 2).
These reactions are presented by system organ class and frequency. Frequencies are defined as: 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); not known (cannot be estimated from the available data)).
Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 2:
Adverse reactions in patients treated with avelumab as monotherapy Frequency Adverse reactions Blood and lymphatic system disorders Very common Anaemia Common Lymphopenia, thrombocytopenia Uncommon Eosinophilia§ Not known Neutropenia* Immune system disorders Very common Infusion-related reaction* Uncommon Hypersensitivity, drug hypersensitivity, sarcoidosis** Rare Anaphylactic reaction, Type I hypersensitivity Endocrine disorders Common Hypothyroidism*, hyperthyroidism* Uncommon Adrenal insufficiency*, autoimmune thyroiditis*, thyroiditis*, autoimmune hypothyroidism* Rare Adrenocortical insufficiency acute*, hypopituitarism* Metabolism and nutrition disorders Very common Decreased appetite Common Hyponatraemia Uncommon Hyperglycaemia* Rare Diabetes mellitus*, Type 1 diabetes mellitus* Nervous system disorders Common Headache, dizziness, neuropathy peripheral Uncommon Myasthenia gravis*†, myasthenic syndrome*† Rare Guillain-Barré Syndrome*, Miller Fisher syndrome* Eye disorders Rare Uveitis* Cardiac disorders Rare Myocarditis* Vascular disorders Common Hypertension Uncommon Hypotension, flushing Respiratory, thoracic and mediastinal disorders Very common Cough, dyspnoea Common Pneumonitis* Rare Interstitial lung disease* Gastrointestinal disorders Very common Nausea, diarrhoea, constipation, vomiting, abdominal pain Common Dry mouth Uncommon Ileus, colitis* Rare Pancreatitis*, autoimmune colitis*, enterocolitis*, autoimmune pancreatitis*, enteritis*, proctitis* Hepatobiliary disorders Uncommon Autoimmune hepatitis* Rare Acute hepatic failure*, hepatic failure*, hepatitis*, hepatotoxicity* Not known Sclerosing cholangitis* Skin and subcutaneous tissue disorders Common Pruritus*, rash*, dry skin, rash maculo-papular* Uncommon Eczema, dermatitis, rash pruritic*, psoriasis*, erythema*, rash erythematous*, rash generalised*, rash macular*, rash papular* Frequency Adverse reactions Rare Erythema multiforme*, purpura*, vitiligo*, pruritus generalised*, dermatitis exfoliative*, pemphigoid*, dermatitis psoriasiform*, drug eruption*, lichen planus* Musculoskeletal and connective tissue disorders Very common Back pain, arthralgia Common Myalgia Uncommon Myositis*, rheumatoid arthritis* Rare Arthritis*, polyarthritis*, oligoarthritis*, Sjogren’s syndrome* Not known Polymyalgia rheumatica* Renal and urinary disorders Uncommon Renal failure*, nephritis* Rare Tubulo-interstitial nephritis*, cystitis noninfective* General disorders and administrative site conditions Very common Fatigue, pyrexia, oedema peripheral Common Asthenia, chills, influenza like illness Rare Systemic inflammatory response syndrome* Investigations Very common Weight decreased Common Blood creatinine increased, blood alkaline phosphatase increased, lipase increased, gamma-glutamyltransferase increased, amylase increased Uncommon Alanine aminotransferase (ALT) increased*, aspartate aminotransferase (AST) increased*, blood creatine phosphokinase increased* Rare Transaminases increased*, thyroxine free decreased*, blood thyroid stimulating hormone increased* * Immune-mediated adverse reaction based on medical review ** Sarcoidosis was observed in clinical studies in patients receiving avelumab in combination with platinum-based chemotherapy § Reaction only observed from study EMR 100070-003 (Part B) after the data cut-off of the pooled analysis, hence frequency estimated # Including cytokine release syndrome with frequency uncommon † Adverse reactions occurred in estimated 4 000 patients exposed to avelumab monotherapy beyond the pooled analysis Renal cell carcinoma Summary of the safety profile The safety of avelumab in combination with axitinib has been evaluated in 489 patients with advanced RCC receiving 10 mg/kg avelumab every 2 weeks and axitinib 5 mg orally twice daily in two clinical studies.
9%). Tabulated list of adverse reactions Adverse reactions reported for 489 patients with advanced RCC treated in two clinical studies or reported from post-marketing use of avelumab in combination with axitinib are presented in Table 3.
These reactions are presented by system organ class and frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); […]