Lenvatinib

Indications

• US label (revised 6/2026): adults with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.
• Test first: ATA 2025 recommends tissue testing for actionable drivers before systemic therapy. NTRK, RET or ALK fusion-targeted drugs are preferred first line when present; BRAF V600E-directed therapy may be used first line when lenvatinib is unsuitable.
• First-line choice: without an actionable driver, lenvatinib or sorafenib is recommended, and lenvatinib is preferred in most cases (ATA 2025, strong).
• Timing (ATA 2025): start without delay if the disease is symptomatic and local therapy is unsuitable. In asymptomatic disease that has progressed over 12–14 months, earlier treatment favours efficacy and later treatment favours quality of life — decide with the patient. Stable or slowly progressive disease can be watched on TSH suppression with imaging every 3–12 months.
• SELECT definition of RAI-refractory: at least one measurable lesion without iodine uptake; progression within 12 months of RAI despite uptake; or cumulative activity >22 GBq (600 mCi) with the last dose at least 6 months before (US label).

Contraindications

• No contraindications in the US label.
• Relative (ATA 2025): uncontrolled hypertension, poor cardiac function, recent acute coronary syndrome or stroke, colitis, diverticulitis, recent bowel surgery or perforation, tumour invading the trachea, oesophagus or great vessels, haemoptysis or a bleeding disorder.
• Major-vessel invasion: serious and fatal carotid haemorrhage has been reported, most often in anaplastic carcinoma. Weigh this where tumour infiltrates the carotid or other large vessels (US label).
• Surgery and wounds: withhold ≥1 week before elective surgery; do not give for ≥2 weeks after major surgery and until the wound has healed (US label).
• Pregnancy and breastfeeding (see below).

• Hypertension: control blood pressure before starting. Check it after 1 week, every 2 weeks for 2 months, then at least monthly (US label); ATA 2025 advises daily home readings. Withhold for grade 3 that persists despite optimal treatment, and resume at a lower dose once ≤ grade 2; stop for grade 4 (US label).
• Choice of antihypertensive: calcium-channel blockers, ACE inhibitors, angiotensin II antagonists, β-blockers and diuretics have all been used; no trial has compared them. Lenvatinib has a short half-life, so review antihypertensives when it is held (ATA 2025).
• Proteinuria: test urine at baseline and periodically. If dipstick is ≥2+, measure 24-h urine protein. Withhold for ≥2 g/24 h; resume at a lower dose once ≤2 g/24 h; stop for nephrotic syndrome (US label).
• Other holds (US label): persistent or intolerable grade 2–3 toxicity, or a grade 4 laboratory abnormality — withhold until grade 0–1, then resume one level lower; grade 4 reaction — stop. QTc >500 ms or a rise >60 ms — withhold until ≤480 ms or baseline, then reduce. Stop for any GI perforation, grade 3–4 fistula or any arterial thromboembolic event.
• The 18 mg start (Study 211): starting at 18 mg failed non-inferiority for response at 24 weeks (40.3% vs 57.3%; odds ratio 0.50) and did not reduce grade ≥3 adverse events (57.1% vs 61.3%). ATA 2025 keeps 24 mg as the standard start (strong), accepting a lower start in selected patients — for example severe renal or hepatic impairment, or hypertension that is hard to control.
• Keep interruptions short: in SELECT, PFS benefit was greater when dose holds took <10% of total treatment time (HR vs placebo 0.14) than when they took ≥10% (HR 0.31).
• Review schedule (ATA 2025): at baseline, at least every 2 weeks for the first 2 months, then every 1–2 months. Check liver function every 2 weeks for 2 months, then monthly (US label).

• Hypertension: 73% in SELECT (grade 3 44%), median onset 16 days (US label). Untreated, it can progress to hypertensive emergency, RPLS, acute kidney injury and heart failure. Treat it promptly rather than stopping the drug — hypertension on treatment was linked to longer survival in SELECT (ATA 2025).
• Proteinuria: 34% in SELECT (grade 3 11%). Renal impairment: 14% (grade 3–5 in 3%, one death); manage diarrhoea and dehydration early to protect the kidneys (US label).
• Diarrhoea: 49% (grade 3 6%) across SELECT and REFLECT; the most frequent reason for interruption or reduction (US label). Symptom diary, low-fat low-fibre diet, fluids and electrolytes; loperamide, then diphenoxylate/atropine (ATA 2025).
• Weight loss, fatigue, poor appetite and stomatitis: common (see SELECT rates above). Dietary, dental and other supportive input before and during treatment can limit them (ATA 2025).
• Thyroid: lenvatinib impairs TSH suppression. Check thyroid function at least monthly and raise levothyroxine as needed (US label).
• Hypocalcaemia: grade 3–4 in 9% in SELECT. Check calcium at least monthly and replace as needed (US label).
• QT prolongation: 9% in SELECT (>500 ms in 2%). Correct electrolytes; monitor the ECG in at-risk patients (US label).
• Bleeding, fistula and perforation: grade 3–5 haemorrhage 2% in SELECT, including one fatal intracranial bleed in a patient with brain metastases; fistula or GI perforation 2% across trials (US label).
• Rare but serious: cardiac dysfunction, arterial thromboembolism, hepatotoxicity, RPLS (0.3%), impaired wound healing and osteonecrosis of the jaw (US label). Across cancers, 1–2% mortality from adverse events has been reported (ATA 2025).

• No radiation precautions apply.
• Women of reproductive potential should use effective contraception during treatment and for 30 days after the last dose (US label).
• Do not breastfeed during treatment and for 1 week after the last dose (US label).
• Osteonecrosis of the jaw is more likely with bisphosphonates, denosumab, dental disease or invasive dental work; tell dentists and surgeons about the drug (US label).
• Swallow capsules whole. For patients who cannot swallow capsules, the label describes how to prepare a suspension (US label).