The incidence rates of treatment-emergent adverse events observed in clinical studies for DTC monotherpahy are presented in table 3 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.
Thyroid Cancer (TC)
The safety of lenvatinib was evaluated in 392 patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) randomized to receive lenvatinib 24 mg once daily (n=261) or placebo (n=131).
Table 3 presents the incidence rates of treatment-emergent adverse events observed in the doubleblind phase of the DTC study. All adverse events occurring with a treatment difference of at least 5% over placebo are included in the Table. Clinically significant events (CSEs) that were observed more frequently than placebo are also included based on an assessment of the known pharmacology of lenvatinib and class effects.
| Table 3 Treatment-Emergent Adverse Events (TEAEs) Reported for Lenvatinib in the Double-Blind Phase of the DTC Study* | ||||
| System Organ Class Preferred Term | Lenvatinib 24 mg N=261 | Placebo N=131 |
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| All Grades (%) |
Grades 3-4 (%) |
All Grades (%) |
Grades 3-4 (%) |
|
| Blood and Lymphatic System Disorders | ||||
| Thrombocytopenia 1 | 13.8 | 1.9 | 2.3 | 0 |
| Lymphopenia 2 | 10.7 | 2.3 | 4.6 | 0.8 |
| Splenic infarction | 0.8 | 0 | 0 | 0 |
| Cardiac Disorders | ||||
| Ejection fraction decreased | 5.4 | 1.1 | 0.8 | 0 |
| Myocardial infarction 3, ‡ | 1.1 | 1.1 | 0.8 | 0.8 |
| Cardiac failure | 0.8 | 0 | 0 | 0 |
| Endocrine Disorders | ||||
| Hypothyroidism | 5.4 | 0 | 0 | 0 |
| Gastrointestinal Disorders | ||||
| Diarrhea | 67.4 | 9.2 | 16.8 | 0 |
| Nausea | 46.7 | 2.3 | 25.2 | 0.8 |
| Stomatitis 4 | 41 | 4.6 | 8.4 | 0 |
| Vomiting | 35.6 | 1.9 | 14.5 | 0 |
| Abdominal pain 5 | 31.4 | 2.3 | 10.7 | 0.8 |
| Constipation | 28.7 | 0.4 | 15.3 | 0.8 |
| Oral pain 6 | 24.9 | 1.1 | 2.3 | 0 |
| Dry mouth | 16.9 | 0.4 | 8.4 | 0 |
| Dyspepsia | 13 | 0.4 | 3.8 | 0 |
| Flatulence | 6.1 | 0 | 0.8 | 0 |
| Anal fistula | 1.1 | 0.4 | 0 | 0 |
| General Disorders and Administration Site Conditions | ||||
| Fatigue | 42.5 | 4.6 | 24.4 | 1.5 |
| Asthenia | 25.3 | 6.1 | 13 | 2.3 |
| Edema peripheral | 20.7 | 0.4 | 7.6 | 0 |
| Malaise | 5.4 | 0 | 0 | 0 |
| Hepatobiliary Disorders | ||||
| Hepatocellular damage / hepatitis 7 | 1.1 | 0.8 | 0 | 0 |
| Infections and Infestations | ||||
| Urinary tract infection | 11.5 | 1.1 | 5.3 | 0 |
| Perineal abscess | 0.8 | 0.8 | 0 | 0 |
| Investigations | ||||
| Weight decreased | 51.3 | 13.4 | 14.5 | 0.8 |
| Electrocardiogram QT prolonged | 8.8 | 1.5 | 1.5 | 0 |
| Alanine aminotransferase increased | 7.7 | 1.5 | 0 | 0 |
| Blood creatinine increased | 7.3 | 0 | 1.5 | 0 |
| Aspartate aminotransferase increased | 6.9 | 1.9 | 1.5 | 0 |
| Blood thyroid stimulating hormone increased | 6.5 | 0 | 0 | 0 |
| Blood alkaline phosphatase increased | 6.1 | 0.8 | 2.3 | 0.8 |
| Blood urea increased | 3.1 | 0 | 0 | 0 |
| Hepatic function abnormal | 2.3 | 0.4 | 0 | 0 |
| Blood bilirubin increased | 1.9 | 0 | 0 | 0 |
| Gamma-glutamyltransferase increased | 1.5 | 0.8 | 0.8 | 0 |
| Metabolism and Nutrition Disorders | ||||
| Decreased appetite | 54.4 | 6.9 | 18.3 | 0.8 |
| Hypokalemia | 13.8 | 3.4 | 3.8 | 0 |
| Hypocalcemia | 12.6 | 5 | 0 | 0 |
| Hypoalbuminemia | 9.6 | 0.4 | 1.5 | 0 |
| Dehydration | 8.8 | 2.3 | 2.3 | 0.8 |
| Hypomagnesemia 8 | 6.5 | 0.4 | 1.5 | 0 |
| Hypercholesterolemia 9 | 5 | 0.4 | 0 | 0 |
| Musculoskeletal and Connective Tissue Disorders | ||||
| Arthralgia | 26.1 | 0.4 | 6.9 | 0.8 |
| Myalgia | 19.2 | 1.5 | 4.6 | 0 |
| Back pain | 17.6 | 1.9 | 9.2 | 0 |
| Musculoskeletal pain | 16.1 | 0.4 | 8.4 | 0.8 |
| Pain in extremity | 15.3 | 1.1 | 6.9 | 1.5 |
| Nervous System Disorders | ||||
| Headache | 38.3 | 3.1 | 11.5 | 0.8 |
| Dysgeusia | 18 | 0 | 3.1 | 0 |
| Dizziness | 15.3 | 0.4 | 9.2 | 0 |
| Monoparesis | 1.1 | 0.8 | 0 | 0 |
| Cerebrovascular accident | 0.8 | 0.4 | 0 | 0 |
| Transient ischemic attack | 0.8 | 0 | 0 | 0 |
| Reversible posterior leukoencephalopathy syndrome | 0.4 | 0 | 0 | 0 |
| Psychiatric Disorders | ||||
| Insomnia | 11.9 | 0 | 3.1 | 0 |
| Renal and Urinary Disorders | ||||
| Proteinuria | 33.7 | 10.7 | 3.1 | 0 |
| Renal failure ‡, 10 | 5 | 2.7 | 0.8 | 0.8 |
| Renal impairment | 1.9 | 0.4 | 0 | 0 |
| Respiratory, Thoracic and Mediastinal Disorders | ||||
| Dysphonia | 31.4 | 1.1 | 5.3 | 0 |
| Cough | 23.8 | 0 | 17.6 | 0 |
| Pulmonary embolism ‡ | 3.1 | 3.1 | 1.5 | 1.5 |
| Skin and Subcutaneous Tissue Disorders | ||||
| Palmar-plantar erythrodysesthesia syndrome | 32.2 | 3.4 | 0.8 | 0 |
| Rash | 18.8 | 0.4 | 1.5 | 0 |
| Alopecia | 12.3 | 0 | 5.3 | 0 |
| Hyperkeratosis | 6.9 | 0 | 1.5 | 0 |
| Palmar erythema | 1.1 | 0 | 0 | 0 |
| Vascular Disorders | ||||
| Hemorrhage ‡, 11 | 34.9 | 1.5 | 18.3 | 3.1 |
| Hypertension 12 | 72.8 | 44.4 | 16 | 3.8 |
| Hypotension | 8.8 | 1.5 | 2.3 | 0 |
| 1. Includes the following terms: thrombocytopenia, platelet count decreased 2. Includes the following terms: lymphopenia, lymphocyte count decreased 3. Includes the following terms: acute myocardial infarction, myocardial infarction 4. Includes the following terms: aphthous stomatitis, stomatitis, glossitis, mouth ulceration, mucosal inflammation 5. Includes the following terms: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, epigastric discomfort, gastrointestinal pain 6. Includes the following terms: oral pain, glossodynia, oropharyngeal pain 7. Includes the following terms: drug-induced liver injury, cholestatic liver injury, hepatic steatosis 8. Includes the following terms: hypomagnesemia, blood magnesium decreased 9. Includes the following terms: hypercholesterolemia and blood cholesterol increased 10. Includes the following terms: acute prerenal failure, renal failure, renal failure acute, renal tubular necrosis 11. Includes the following terms: epistaxis, hematuria, contusion, gingival bleeding, hematochezia, pulmonary hemorrhage, vaginal hemorrhage, rectal hemorrhage, hematoma, hemorrhoidal hemorrhage, laryngeal hemorrhage, petechiae, intracranial tumor hemorrhage, hemorrhagic stroke, pleural hemorrhage, splenic hemorrhage, blood urine present, conjunctival hemorrhage, eye hemorrhage, gastroduodenitis hemorrhagic, hematemesis, increased tendency to bruise, proctitis hemorrhagic, purpura, renal hematoma, skin hemorrhage, splinter hemorrhages 12. Includes the following terms: hypertension, hypertensive crisis, blood pressure diastolic increased, blood pressure increased |
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