Lenvatinib Side Effects
Lenvatinib causes adverse events in nearly all patients, with the most common being hypertension (occurring in 67-73% of patients), diarrhea (39-67%), fatigue (62-67%), decreased appetite (50-54%), weight loss (46-51%), proteinuria (31-34%), and hand-foot skin reaction (3-32%), with serious grade ≥3 adverse events requiring dose reduction in 68% of patients. 1
Common Adverse Events (Any Grade)
Vascular and Cardiovascular Toxicities
- Hypertension: 67-73% (grade ≥3: 23-44%) - most frequent adverse event 2, 1
- Hypotension: 9% 1
- QT interval prolongation: 9% (grade ≥3: 2%) 1
Gastrointestinal Toxicities
- Diarrhea: 39-67% (grade ≥3: 8-9%) 2, 1
- Nausea: 47% 1
- Stomatitis/oral mucositis: 41% (grade ≥3: 5%) 1
- Vomiting: 36% 1
- Abdominal pain: 31% 1
- Decreased appetite: 50-54% 1
- Constipation: 29% 1
Constitutional Symptoms
Renal and Urinary
Dermatologic
- Hand-foot skin reaction (palmar-plantar erythrodysesthesia): 3-32% (grade ≥3: 3%) - notably lower than sorafenib (11%) 2, 1
- Rash: 21% 1
- Alopecia: 3-12% (much lower than sorafenib at 25%) 2, 1
Endocrine and Metabolic
- Hypothyroidism: 16% (significantly higher than sorafenib at 2%) 2, 1
- Hypertriglyceridemia: 70% 1
- Hypocalcemia: 40% (grade ≥3: 9%) 1
- Hypokalemia: 34% (grade ≥3: 6-10%) 1
Respiratory
Musculoskeletal
- Arthralgia/myalgia: 62% (grade ≥3: 5%) 1
Neurologic
Serious Adverse Events (Grade ≥3)
The most common serious adverse events include:
- Hypertension: 23-44% 2, 1
- Proteinuria: 6-11% 2, 1
- Fatigue: 11% 1
- Weight loss: 13% 1
- Decreased appetite: 10% 1
- Diarrhea: 8-9% 1
Laboratory Abnormalities (Grade 3-4)
- Hypocalcemia: 9% 1
- Hypokalemia: 6% 1
- Increased AST: 5% 1
- Increased ALT: 4% 1
- Increased lipase: 4-14% 1
- Thrombocytopenia: 2-8% 1
- Lymphopenia: 18% 1
Rare but Serious Toxicities
Life-Threatening Events
- Treatment-related deaths: 6 deaths occurred in thyroid cancer trials 3
- Arterial thromboembolism: 5% 1
- Pulmonary embolism: 3% 1
- Arterial aneurysms, dissections, and rupture (postmarketing) 1
- Hemorrhagic events 1
- Gastrointestinal perforation and fistula formation 1
Organ-Specific Serious Events
- Hepatotoxicity: hepatic failure, hepatic encephalopathy 1
- Renal failure and impairment 1
- Reversible posterior leukoencephalopathy syndrome (RPLS) 1
- Osteonecrosis of the jaw: 0.4% 1
- Acalculous cholecystitis (increasingly recognized, not as rare as initially thought) 4
- Pancreatitis (postmarketing) 1
- Nephrotic syndrome (postmarketing) 1
Cardiac
Treatment Modifications
Dose reductions are required in 68% of patients 1, with the most common reasons being:
Treatment discontinuation due to adverse events: 15-18% of patients 1, 5
Patients receiving lenvatinib are more likely to discontinue treatment due to adverse events compared to sorafenib (relative risk 1.46) 2
Age-Related Considerations
Patients aged >65 years have higher rates of grade ≥3 adverse effects but maintain progression-free survival benefit, suggesting lenvatinib is appropriate for all ages with careful monitoring 3
Key Clinical Pitfalls
- Nearly universal occurrence: Any-grade treatment-emergent adverse events occur in nearly all patients receiving lenvatinib 3
- Proactive monitoring essential: Due to high AE risk, prophylactic measures and regular monitoring are mandatory 6
- Maintain highest tolerable dose: Disease progression may occur with suboptimal dosing after reduction; maintain highest possible dose when managing AEs 6
- Distinct toxicity profile vs sorafenib: Lower hand-foot syndrome (3% vs 11%) but higher hypertension (23% vs 14%), proteinuria (6% vs 2%), and hypothyroidism (16% vs 2%) 2
- Acalculous cholecystitis underrecognized: Emerging evidence suggests this is more common than licensing studies indicated 4