Lenvatinib

Lenvatinib is an oral anticancer medicine belonging to the tyrosine kinase inhibitor class. It works by blocking several receptor tyrosine kinases involved in tumour growth, new blood vessel formation, and cancer progression. These include vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), platelet-derived growth factor receptor alpha (PDGFRα), and other signalling targets. By interfering with these pathways, lenvatinib can reduce tumour-associated blood vessel formation and help slow cancer growth.

Lenvatinib is available as oral capsules and is used either alone or in combination with other anticancer medicines, depending on the cancer type and treatment setting. Its established clinical applications include selected cases of differentiated thyroid cancer, advanced renal cell carcinoma, unresectable hepatocellular carcinoma, and advanced endometrial carcinoma. The approved indications and combination regimens differ between countries and may change as new evidence and regulatory decisions emerge.

Treatment requires specialist supervision because lenvatinib can cause significant adverse effects, including high blood pressure, protein in the urine, diarrhoea, fatigue, and liver abnormalities. Dosing depends on the indication, body weight in certain liver cancer regimens, combination therapy, organ function, and treatment tolerance. Regular clinical assessments and laboratory monitoring are essential to support safe treatment and determine whether dose modification or interruption is necessary.

Lenvatinib was developed as a targeted anticancer agent designed to inhibit multiple receptor tyrosine kinases involved in angiogenesis and tumour signalling. The US Food and Drug Administration (FDA) granted its first approval in 2015 for selected patients with radioactive iodine-refractory differentiated thyroid cancer. The European Medicines Agency (EMA) recommended its initial authorisation in March 2015, with European Commission marketing authorisation granted in June 2015. Subsequent regulatory decisions expanded its clinical use to include unresectable hepatocellular carcinoma, advanced renal cell carcinoma in combination regimens, and selected advanced endometrial cancers. In the United States, lenvatinib is marketed as Lenvima; in the European Union, lenvatinib-containing products include Lenvima and Kisplyx, with indications depending on the product and treatment combination. Evidence supporting its use comes from clinical programmes including SELECT in thyroid cancer, REFLECT in hepatocellular carcinoma, Study 205 in renal cell carcinoma, and Study 309/KEYNOTE-775 in endometrial cancer. Approval status and indications in India should be checked against current Central Drugs Standard Control Organisation (CDSCO/DCGI) authorisations and the locally approved product information.

Lenvatinib is used to treat selected malignancies according to the applicable national product label. As monotherapy, it is indicated for adults with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer and for first-line treatment of unresectable hepatocellular carcinoma. In advanced renal cell carcinoma, it may be used with pembrolizumab as first-line treatment or with everolimus after prior anti-angiogenic therapy, depending on the applicable approval. In selected patients with advanced endometrial carcinoma that has progressed after previous systemic treatment and is not suitable for curative surgery or radiation, lenvatinib is used in combination with pembrolizumab. Eligibility depends on the tumour type, disease stage, previous treatment, molecular or mismatch-repair status where relevant, and local regulatory requirements. Not every regimen is approved in every country, and lenvatinib should only be prescribed for an appropriate indication by a qualified oncology specialist.

Lenvatinib is administered orally, usually once daily, and may generally be taken with or without food at a consistent time. The recommended adult dose depends on the indication and treatment regimen. For differentiated thyroid cancer, the standard starting dose is commonly 24 mg once daily. For unresectable hepatocellular carcinoma, dosing is based on body weight, generally 12 mg once daily for patients weighing at least 60 kg and 8 mg once daily for those weighing less than 60 kg. For advanced renal cell carcinoma, recommended regimens include 20 mg once daily with pembrolizumab or 18 mg once daily with everolimus 5 mg once daily. In advanced endometrial carcinoma, the commonly approved US regimen is 20 mg once daily with pembrolizumab. These are indication-specific reference regimens, not individual treatment recommendations. Dose reductions or temporary interruptions may be required for adverse reactions or severe renal or hepatic impairment. Treatment is generally continued until disease progression, unacceptable toxicity, or another clinical reason to discontinue. Patients should not alter or stop treatment without medical advice.

Common side effects of lenvatinib include high blood pressure, tiredness, diarrhoea, reduced appetite, weight loss, nausea, vomiting, abdominal discomfort, mouth sores, and protein in the urine. Some patients may develop hypothyroidism, headache, joint or muscle pain, or changes in liver and kidney function. The frequency and severity of adverse effects vary with the cancer being treated, dose, combination medicines, and individual health status. Many side effects can be managed through supportive care, blood pressure treatment, hydration, nutritional support, laboratory monitoring, or medically supervised dose adjustments. Patients should report persistent diarrhoea, reduced food or fluid intake, worsening fatigue, or other new symptoms promptly so that complications can be assessed and treated early.

Lenvatinib can cause serious adverse reactions, including severe hypertension, cardiac dysfunction, arterial thromboembolic events, significant liver injury, kidney impairment, gastrointestinal perforation, and fistula formation. Haemorrhage, prolonged QT interval, posterior reversible encephalopathy syndrome (PRES), impaired wound healing, and severe proteinuria are additional recognised risks. In some patients, these complications may require treatment interruption, dose reduction, or permanent discontinuation. Blood pressure should be controlled before treatment begins and monitored regularly. Liver function, renal function, electrolytes, and urinary protein should be assessed during therapy. Patients experiencing chest pain, sudden weakness, severe headache with visual changes, major bleeding, severe abdominal pain, or breathing difficulty require urgent medical evaluation. Lenvatinib should be permanently discontinued for certain severe toxicities in accordance with the applicable prescribing information. There are no universal absolute contraindications listed in the US prescribing information, but individual risks and combination-treatment restrictions must be assessed by the treating specialist.

Before starting lenvatinib, clinicians should assess blood pressure, renal and hepatic function, electrolytes, thyroid function, and urinary protein, together with cardiovascular history, bleeding risk, nutritional status, and current medicines. Pregnancy should be avoided during treatment because lenvatinib may cause fetal harm; appropriate contraception and pregnancy counselling are important where applicable. Breastfeeding recommendations should follow the current local prescribing information. Caution is needed in patients with significant cardiovascular disease, pre-existing hypertension, impaired kidney or liver function, or a history of gastrointestinal complications. Lenvatinib may affect cardiac electrical activity through QT prolongation, making electrolyte abnormalities and other QT-prolonging medicines clinically relevant. Drug interactions can occur through effects on drug-metabolising enzymes and transport pathways, and medicines with a narrow therapeutic index require particular review. Because lenvatinib is a small-molecule medicine rather than a biologic, conventional pharmacokinetic interactions are relevant. Vaccination schedules should be reviewed, especially when lenvatinib is combined with immunotherapy; live vaccines require particular caution during immunosuppressive cancer treatment.

Before dispensing lenvatinib, confirm the indication, prescribed dose, combination partner, relevant organ-function adjustments, and current local product information. Document baseline blood pressure, thyroid function, renal and hepatic parameters, electrolytes, and urinary protein, then establish a monitoring schedule appropriate to the patient's risk and treatment regimen. Counsel patients to take the medicine consistently, follow the prescribed instructions for missed doses, and avoid doubling a dose to compensate for a missed one. Review potential interactions, including medicines that can prolong the QT interval, and reinforce home blood pressure monitoring when appropriate. Patients should understand when to contact their oncology team and which symptoms require urgent assessment. Pharmacists should verify dose changes after toxicity, check adherence and tolerability, and coordinate with the oncology team when treatment is interrupted or restarted. For combination regimens, monitoring must also address the risks associated with the partner medicine, particularly immune-mediated adverse events when pembrolizumab is used. Dose modification and treatment discontinuation should follow the current approved prescribing information and specialist judgement.