The incidence rates of treatment-emergent adverse events observed in clinical studies for HCC are presented in table 7 below.
Events are included as Adverse Drug Reactions (ADRs) based on the incidence rates of treatment emergent adverse events (TEAEs) in the placebo-controlled DTC study together with events from other indications assessed in the context of TEAE incidence rates across study treatment arms, the known pharmacology of lenvatinib and the underlying indication.
A multicenter, randomized, open-label study was conducted to determine the safety and efficacy of lenvatinib compared to sorafenib in subjects with unresectable hepatocellular carcinoma (HCC). Subjects were randomized 1:1 to lenvatinib (12 mg [≥ 60 kg BW] or lenvatinib 8 mg [<60 kg BW]) orally, once daily, or sorafenib 400 mg orally, twice daily.
Table 7 presents the incidence rates of treatment emergent adverse events observed in the HCC study and includes all adverse events occurring with a frequency of at least 10% and of at least 3% ≥ CTCAE Grade 3.
| Table 7 Treatment Emergent Adverse Events with Frequency ≥10% All Grades or Frequency ≥3% ≥Grade 3 by System Organ Class and Preferred Term in Study 304 (HCC) | ||||
| System Organ Class Preferred Term | HCC Randomized Safety Set Lenvatinib (N=476) n (%) |
HCC Randomized Safety Set Sorafenib (N=475) n (%) |
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| Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | |
| Blood and lymphatic system disorders | ||||
| Thrombocytopenia 1 | 119 (25.0) | 35 (7.4) | 86 (18.1) | 22 (4.6) |
| Leukopenia 2 | 58 (12.2) | 13 (2.7) | 35 (7.4) | 9 (1.9) |
| Nuetropenia 3 | 56 (11.8) | 21 (4.4) | 18 (3.8) | 8 (1.7) |
| Anemia 4 | 36 (7.6) | 16 (3.4) | 45 (9.5) | 17 (3.6) |
| Endocrine Disorders | ||||
| Hypothyroidism | 78 (16.4) | 0 | 8 (1.7) | 0 |
| Gastrointestinal Disorders | ||||
| Diarrhoea | 184 (38.7) | 20 (4.2) | 220 (46.3) | 20 (4.2) |
| Abdominal pain 5 | 143 (30.0) | 14 (2.9) | 131 (27.6) | 18 (3.8) |
| Nausea | 93 (19.5) | 4 (0.8) | 68 (14.3) | 4 (0.8) |
| Vomiting | 77 (16.2) | 6 (1.3) | 36 (7.6) | 5 (1.1) |
| Constipation | 76 (16.0) | 3 (0.6) | 52 (10.9) | 0 |
| Ascites | 68 (14.3) | 18 (3.8) | 44 (9.3) | 14 (2.9) |
| Stomatitis 6 | 53 (11.1) | 2 (0.4) | 65 (13.7) | 3 (0.6) |
| General Disorders and Administration Site Conditions | ||||
| Fatigue | 141 (29.6) | 18 (3.8) | 119 (25.1) | 17 (3.6) |
| Pyrexia | 69 (14.5) | 0 | 63 (13.3) | 1 (0.2) |
| Oedema peripheral | 66 (13.9) | 4 (0.8) | 33 (6.9) | 1 (0.2) |
| Asthenia | 54 (11.3) | 14 (2.9) | 48 (10.1) | 11 (2.3) |
| Hepatobiliary Disorders | ||||
| Hyperbilirubinemia 7 | 82 (17.2) | 37 (7.8) | 75 (15.8) | 28 (5.9) |
| Hypoalbunimia 8 | 57 (12.0) | 5 (1.1) | 47 (9.9) | 2 (0.4) |
| Hepatic encephalopathy 9 | 40 (8.4) | 26 (5.5) | 13 (2.7) | 9 (1.9) |
| Hepatic failure i0 | 17 (3.6) | 17 (3.6) | 12 (2.5) | 12 (2.5) |
| Investigations | ||||
| Weight decreased | 147 (30.9) | 36 (7.6) | 106 (22.3) | 14 (2.9) |
| Aspartate aminotransferase increased | 65 (13.7) | 24 (5.0) | 80 (16.8) | 38 (8.0) |
| Alanine aminotransferase increased | 53 (11.1) | 16 (3.4) | 52 (10.9) | 16 (3.4) |
| Gamma-glutamyltransferase increased |
37 (7.8) | 26 (5.5) | 26 (5.5) | 19 (4.0) |
| Metabolism and Nutrition Disorders | ||||
| Decreased appetite | 162 (34.0) | 22 (4.6) | 127 (26.7) | 6 (1.3) |
| Hyponatremia 11 | 27 (5.7) | 23 (4.8) | 10 (2.1) | 10 (2.1) |
| Musculoskeletal and Connective Tissue Disorders | ||||
| Back pain | 50 (10.5) | 1 (0.2) | 31 (6.5) | 5 (1.1) |
| Renal and Urinary Tract Disorders | ||||
| Proteinuria | 117 (24.6) | 27 (5.7) | 54 (11.4) | 8 (1.7) |
| Respiratory and Mediastinal Disorders | ||||
| Dysphonia | 113 (23.7) | 1 (0.2) | 57 (12.0) | 0 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Palmar-plantar erythrodysaesthesia syndrome |
128 (26.9) | 14 (2.9) | 249 (52.4) | 54 (11.4) |
| Vascular Disorders | ||||
| Hypertension 12 | 212 (44.5) | 112 (23.5) | 147 (30.9) | 69 (14.5)) |
| Hemorrhagic events 13 | 117 (24.6) | 24 (5.0) | 76 (16.0) | 22 (4.6) |
| 1 Includes the terms: platelet count decreased, thrombocytopenia. 2 Includes the terms: leukopenia, white blood cell count decreased. 3 Includes the terms: neutropenia, neutrophil count decreased. 4 Includes the terms: anaemia, haemoglobin decreased. 5 Includes the terms: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, epigastric discomfort, gastrointestinal pain. 6 Includes the terms: aphthous ulcer, gingival erosion, gingival ulceration, glossitis, mouth ulceration, oral mucosal blistering, stomatitis. 7 Includes the terms: bilirubin conjugated increased, blood bilirubin increased, hyperbilirubinaemia, jaundice. 8 Includes the terms: blood albumin decreased, hypoalbuminaemia 9 Includes the terms: coma hepatic, encephalopathy, hepatic encephalopathy, metabolic encephalopathy. 10 Includes the terms: acute hepatic failure, chronic hepatic failure, hepatic failure. 11 Includes the terms: blood sodium decreased, hyponatraemia. 12 Includes the terms: blood pressure diastolic increased, blood pressure increased, hypertension, orthostatic hypertension. 13 Includes all terms reported to the MedDRA 19.1 Standard MedDRA Query Haemorrhage terms (excluding laboratory terms) (Narrow scope). |
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