4). Trifluridine/ Tipiracil as monotherapy The safety profile of trifluridine/ tipiracil as monotherapy is based on the pooled data from 1114 patients with metastatic colorectal or gastric cancer in controlled phase III clinical studies.
The most common adverse reactions (≥ 30%) are neutropenia (53% [34% ≥ Grade 3]), nausea (31 % [1% ≥ Grade 3]), fatigue (31% [4% ≥ Grade 3]), and anaemia (30 % [11% ≥ Grade 3]). The most common adverse reactions (≥ 2%) that resulted in treatment discontinuation, dose reduction, dose delay, or dose interruption were neutropenia, anaemia, fatigue, leukopenia, thrombocytopenia, diarrhoea, and nausea.
Trifluridine/ Tipiracil in combination with bevacizumab The safety profile of trifluridine/ tipiracil in combination with bevacizumab is based on the data from 246 patients with metastatic colorectal cancer in the controlled phase III clinical study (SUNLIGHT).
The most common adverse reactions (≥ 30%) are neutropenia (69% [48% ≥ Grade 3]), fatigue (35% [3% ≥ Grade 3]), and nausea (33% [1% ≥ Grade 3]). The most common adverse reactions (≥ 2%) that resulted in treatment discontinuation, dose reduction, dose delay, or dose interruption of trifluridine/ tipiracil when used in combination with bevacizumab were neutropenia, fatigue, thrombocytopenia, nausea and anaemia.
When trifluridine/ tipiracil is used in combination with bevacizumab, the frequency of the following adverse reactions was increased compared to trifluridine/ tipiracil as monotherapy: neutropenia (69% vs 53%), severe neutropenia (48% vs 34%), thrombocytopenia (24% vs 16%), stomatitis (11% vs 6%).
The adverse reactions observed from the 533 treated patients with metastatic colorectal cancer in the placebo-controlled Phase III (RECOURSE) clinical study, the 335 treated patients with metastatic gastric cancer in the placebo- controlled Phase III (TAGS) clinical study, the 246 patients treated with trifluridine/ tipiracil in monotherapy and the 246 patients treated with trifluridine/ tipiracil in combination with bevacizumab for metastatic colorectal cancer in the controlled Phase III (SUNLIGHT) clinical study are shown in Table 6.
They are classified according to System Organ Class (SOC) and the appropriate Medical Dictionary for Regulatory (MedDRA) term is used to describe a certain drug reaction and its synonyms and related conditions. Adverse reactions known to occur with trifluridine/ tipiracil given alone or with bevacizumab may occur during treatment with these medicinal products in combination, even if these reactions were not reported in clinical trials with combination therapy.
Adverse reactions are grouped according to their frequencies. Frequency groups are defined by the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥1/1,000 to < 1/100); and rare (≥ 1/10 000 to < 1/1 000).
Within each frequency group, adverse drug reactions are presented in order of decreasing seriousness. Table 6 – Adverse reactions reported in clinical studies in patients treated with Trifluridine/ Tipiracil System Organ Class (MedDRA)a Adverse reactions Frequency Monotherapy Combination with bevacizumab Infections and infestations Lower respiratory tract Common - infection Neutropenic sepsis Uncommon - Biliary tract infection Uncommon - Infection Uncommon Common Urinary tract infection Uncommon Uncommon Bacterial infection Uncommon - Candida infection Uncommon - Conjunctivitis Uncommon - Herpes zoster Uncommon - Influenza Uncommon - Upper respiratory tract Uncommon - infection Enteritis infectious Rare - Septic shockb Rare - Gingivitis Rare Uncommon Tinea pedis Rare - Neoplasms benign, malignant Cancer pain and unspecified (incl cysts and polyps) Uncommon - Blood and lymphatic system Anaemia Very common Very common disorders Neutropenia Very common Very common Leukopenia Very common Common Thrombocytopenia Very common Very common Febrile neutropenia Common Uncommon Lymphopenia Common Common Pancytopenia Uncommon Uncommon Erythropenia Uncommon - Leukocytosis Uncommon - Monocytopenia Uncommon - Monocytosis Uncommon - Granulocytopenia Rare - Metabolism and nutrition disorders Hypoalbuminaemia Very common Very common Dehydration Common Uncommon Hyperglycaemia Uncommon - Hyperkalaemia Uncommon Uncommon Hypocalcaemia Uncommon - Hypokalaemia Uncommon - Hyponatraemia Uncommon - Hypophosphataemia Uncommon - Gout Uncommon - Hypernatraemia Rare - Psychiatric disorders Anxiety Uncommon - Insomnia Uncommon - Nervous system disorders Dysgeusia Common Common Dizziness Uncommon Common Headache Uncommon Common Neuropathy peripheral Uncommon Uncommon Paraesthesia Uncommon Uncommon Lethargy Uncommon - Neurotoxicity Uncommon - Burning sensation Rare - Dysaesthesia Rare - Hyperaesthesia Rare - Hypoaesthesia Rare - Syncope Rare - Eye disorders Cataract Rare - Diplopia Rare - Dry eye Rare - Vision blurred Rare - Visual acuity reduced Rare - Ear and labyrinth disorders Vertigo Uncommon - Ear discomfort Rare - Cardiac disorders Angina pectoris Uncommon - Arrhythmia Uncommon - Palpitations Uncommon - Vascular disorders Hypertension Uncommon Common Flushing Uncommon - Hypotension Uncommon - Embolism Rare - Respiratory, thoracic and Dyspnoea Common Common mediastinal disorders Pulmonary embolismb Uncommon - Dysphonia Uncommon Uncommon Cough Uncommon - Epistaxis Uncommon - Rhinorrhoea Rare Uncommon Oropharyngeal pain Rare - Pleural effusion Rare - Gastrointestinal disorders Diarrhoea Very common Very common Vomiting Very common Very common Nausea Very common Very common Abdominal pain Common Common Stomatitis Common Very common Constipation Common Common Ileus Uncommon - Gastrointestinal haemorrhage Uncommon - Colitis Uncommon Uncommon Mouth ulceration Uncommon Common Oral disorder Uncommon Common Abdominal distension Uncommon […]