Lenvatinib (Lenvima): A Multi-Kinase Inhibitor for Advanced Cancers
Lenvatinib is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), RET, and KIT proto-oncogenes, approved for treatment of advanced hepatocellular carcinoma (HCC), differentiated thyroid cancer, renal cell carcinoma, and endometrial carcinoma. 1
FDA-Approved Indications
- Differentiated thyroid cancer (DTC) - Used as monotherapy for DTC that can no longer be treated with radioactive iodine and is progressing 2
- Advanced renal cell carcinoma (RCC) - Used in two scenarios:
- Hepatocellular carcinoma (HCC) - Used as first-line treatment for unresectable HCC 3, 2
- Advanced endometrial carcinoma (EC) - Used with pembrolizumab for pMMR or non-MSI-H tumors when:
- Prior anti-cancer treatment is no longer working
- Cancer cannot be cured by surgery or radiation 2
Mechanism of Action
- Inhibits multiple receptor tyrosine kinases involved in tumor angiogenesis and proliferation 4, 5
- Primary targets include:
Clinical Efficacy
In Hepatocellular Carcinoma (HCC)
- In the REFLECT trial, lenvatinib demonstrated non-inferiority to sorafenib in overall survival (13.6 vs. 12.3 months) 3
- Showed superior progression-free survival (7.4 vs. 3.7 months) and time to progression (8.9 vs. 3.7 months) compared to sorafenib 1
- Significantly higher objective response rate (24.1% vs. 9.2%) compared to sorafenib 1
In Renal Cell Carcinoma (RCC)
- The CLEAR trial showed lenvatinib plus pembrolizumab significantly improved progression-free survival and objective response rate compared to sunitinib 3
- This combination is now a category 1, preferred treatment option for patients with clear cell RCC across all risk groups 3
Dosing and Administration
- Weight-based dosing for HCC: 12 mg daily for patients ≥60 kg; 8 mg daily for patients <60 kg 1
- Taken once daily with or without food 2
- Capsules should be swallowed whole or can be mixed with water/apple juice if swallowing difficulties exist 2
- Dose modifications may be required based on adverse events 2
Common Adverse Events
- Hypertension (42% of patients, grade 3/4 in 23%) - requires regular blood pressure monitoring 6
- Diarrhea (39% of patients) 6
- Decreased appetite (34%) and weight loss (31%) 6
- Hand-foot skin reaction (27%) - less common than with sorafenib (52%) 1, 6
- Fatigue (30%) 6
- Proteinuria (25%) 6
- Hypothyroidism (16%) - requires regular thyroid function monitoring 6
Management of Adverse Events
- Regular monitoring of blood pressure, thyroid function, and proteinuria is essential 6
- Adverse events often lead to treatment interruptions (82.4% of patients) and dose reductions (67.8%) 6
- Most adverse events occur during the first few weeks of treatment and decrease after treatment interruption 6
- For grade 1-2 adverse events, dose interruption is generally not required 7
- For persistent/intolerable grade 2 or grade 3 adverse events, treatment should be interrupted until symptoms improve to grade 0-1 7
Special Considerations
- Only recommended for HCC patients with Child-Pugh A liver function 3, 1
- Not recommended for patients with main portal vein invasion or >50% tumor to liver volume occupancy 1
- Should be stopped at least 1 week before planned surgery due to potential impairment of wound healing 2
- Contraindicated in pregnancy - can harm the unborn baby 2
- Breastfeeding should be discontinued during treatment and for 1 week after the last dose 2
Drug Interactions
- Limited clinically significant drug interactions due to multiple metabolic pathways 4
- Special caution with osteoporosis medications due to risk of osteonecrosis of the jaw 2
Lenvatinib represents an important treatment option across multiple advanced cancers, with demonstrated efficacy and a manageable side effect profile when properly monitored.