The incidence rates of treatment-emergent adverse events observed in clinical studies for RCC in combination with everolimus are presented in the table 6 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.
RCC 2L Combination With Everolimus
A multicenter, randomized, open-label, trial was conducted to determine the safety and efficacy of lenvatinib administered alone or in combination with everolimus in subjects with unresectable, advanced or metastatic RCC. The study consisted of a Phase 1b dose finding and a Phase 2 portion.
The Phase 2 portion enrolled a total of 153 patients with advanced or metastatic renal cell carcinoma (RCC) following 1 prior VEGF-targeted treatment who were randomized to receive the combination of 18 mg lenvatinib plus 5 mg everolimus (n=51), lenvatinib 24 mg (n=52) or everolimus 10 mg (n=50) once daily).
Table 6 presents the incidence rates of treatment-emergent adverse events observed in the RCC study.
All adverse events occurring with a frequency of at least 10% all Grades or 3% Grade 3 or 4.
| Table 6 Treatment-Emergent Adverse Events with Frequency >10 All Grades or >3% Grade 3 and 4 by System Organ Class and Preferred Term Safety Analysis in Study 205 (RCC) | ||||||
| System Organ Class Preferred Term |
Lenvatinib 18 mg + Everolimus 5 mg (N=51) |
Lenvatinib 24 mg (N=52) |
Everolimus 10 mg (N=50) |
|||
| All Grades (%) |
Grades ≥3 (%) |
All Grades (%) |
Grades ≥3 (%) |
All Grades (%) |
Grades ≥3 (%) |
|
| Blood and Lymphatic System Disorders | ||||||
| Anemia | 17.6 | 7.8 | 7.7 | 1.9 | 26 | 12.012 |
| Thrombocytopenia 1 | 9.8 | 5.9 | 1.9 | 0 | 8 | 0 |
| Endocrine Disorders | ||||||
| Hypothyroidism | 23.5 | 0 | 36.5 | 1.9 | 2 | 0 |
| Gastrointestinal Disorders | ||||||
| Abdominal pain 2 | 39.2 | 3.9 | 32.7 | 3.8 | 8 | 0 |
| Constipation | 11.8 | 0 | 36.5 | 0 | 18 | 0 |
| Diarrhea | 84.3 | 19.6 | 71.2 | 11.5 | 34 | 2 |
| Dyspepsia | 11.8 | 0 | 11.5 | 1.9 | 12 | 0 |
| Nausea | 43.1 | 5.9 | 61.5 | 7.7 | 16 | 0 |
| Oral inflammation 2 | 39.2 | 0 | 26.9 | 1.9 | 50 | 4 |
| Oral pain 2 | 17.6 | 0 | 13.5 | 0 | 4 | 0 |
| Vomiting | 47.1 | 7.8 | 38.5 | 3.8 | 12 | 0 |
| General Disorders and Administration Site Conditions | ||||||
| Asthenia | 25.5 | 3.9 | 15.4 | 1.9 | 6 | 2 |
| Fatigue | 51 | 11.8 | 40.4 | 7.7 | 32 | 0 |
| General physical health deterioration | 3.9 | 3.9 | 0 | 0 | 0 | 0 |
| Edema peripheral | 29.4 | 0 | 17.3 | 0 | 18 | 0 |
| Pyrexia | 21.6 | 2 | 9.6 | 0 | 10 | 2 |
| Infections and Infestations | ||||||
| Nasopharyngitis | 11.8 | 0 | 7.7 | 0 | 12 | 0 |
| Investigations | ||||||
| Blood thyroid stimulating hormone increased | 13.7 | 0 | 3.8 | 0 | 2 | 0 |
| Lipase Increased | 7.8 | 3.9 | 11.5 | 7.7 | 6 | 4 |
| Weight decreased | 31.4 | 2 | 50 | 5.8 | 8 | 0 |
| Metabolism and Nutrition Disorders | ||||||
| Decreased appetite | 52.9 | 5.9 | 57.7 | 3.8 | 18 | 0 |
| Dehydration | 9.8 | 5.9 | 1.9 | 0 | 2 | 0 |
| Hypercholesterolaemia 5 | 35.3 | 2 | 11.5 | 1.9 | 16 | 0 |
| Hyperglycemia | 15.7 | 0 | 5.8 | 0 | 24 | 10 |
| Hypertriglyceridemia | 35.3 | 9.8 | 13.5 | 3.8 | 24 | 8 |
| Hypocalcaemia | 7.8 | 3.9 | 5.8 | 0 | 4 | 0 |
| Hypokalemia | 13.7 | 3.9 | 1.9 | 1.9 | 2 | 0 |
| Musculoskeletal and Connective Tissue Disorders | ||||||
| Arthralgia | 29.4 | 0 | 25 | 0 | 14 | 0 |
| Back pain | 21.6 | 3.9 | 21.2 | 0 | 14 | 0 |
| Musculoskeletal chest pain | 17.6 | 2 | 15.4 | 3.8 | 4 | 0 |
| Pain in extremity | 11.8 | 0 | 11.5 | 1.9 | 6 | 0 |
| Nervous System Disorders | ||||||
| Headache | 17.6 | 2 | 26.9 | 5.8 | 10 | 2 |
| Psychiatric Disorders | ||||||
| Confusional state | 3.9 | 3.9 | 3.8 | 1.9 | 0 | 0 |
| Insomnia | 17.6 | 2 | 15.4 | 0 | 2 | 0 |
| Renal and Urinary Disorders | ||||||
| Proteinuria | 23.5 | 3.9 | 30.8 | 19.2 | 14 | 2 |
| Renal failure 6 | 5.9 | 5.9 | 9.6 | 5.8 | 2 | 2 |
| Respiratory, Thoracic and Mediastinal Disorders | ||||||
| Cough | 39.2 | 0 | 17.2 | 1.9 | 30 | 0 |
| Dysphonia | 19.6 | 0 | 36.5 | 0 | 4 | 0 |
| Dyspnea | 23.5 | 2 | 23.1 | 1.9 | 22 | 8 |
| Skin and Subcutaneous Tissue Disorders | ||||||
| Pruritus | 13.7 | 0 | 5.8 | 0 | 14 | 0 |
| Rash | 17.6 | 0 | 15.4 | 0 | 22 | 0 |
| Vascular Disorders | ||||||
| Hemorrhagic events 7 | 33.3 | 5.9 | 28.8 | 1.9 | 28 | 2 |
| Hypertension 8 | 41.2 | 13.7 | 48.1 | 17.3 | 10 | 2 |
| 1. Includes the following terms: thrombocytopenia, platelet count decreased 2. Includes the following terms: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, epigastric discomfort, gastrointestinal pain 3. Includes the following terms: aphthous stomatitis, stomatitis, glossitis, mouth ulceration, mucosal inflammation 4. Includes the following terms: oral pain, glossodynia, oropharyngeal pain 5. Includes the following terms: hypercholesterolemia, blood cholesterol increased 6. Includes the following terms: acute prerenal failure, renal failure, renal failure acute, renal tubular necrosis 7. Includes the following terms: bone contusion, cerebral hemorrhage, contusion, diarrhea hemorrhagic, ecchymosis, epistaxis, eye contusion, eyelid hematoma, gastric hemorrhage, gastrointestinal hemorrhage, gingival bleeding, hemarthrosis, hematoma, hematuria, hemoptysis, hemorrhage intracranial, hemorrhagic disorder, lip hemorrhage, periorbital contusion, petechiae, renal hematoma, scrotal hematocoele 8. Includes the following terms: hypertension, hypertensive crisis, blood pressure diastolic increased, blood pressure increased, blood pressure systolic increased |
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