Sorafenib

Indications

• US label (revised 8/2023): locally recurrent or metastatic, progressive DTC refractory to radioactive iodine treatment.
• ATA 2025: test tumour tissue for actionable drivers first. Without one, lenvatinib or sorafenib is recommended (strong); lenvatinib is preferred in most cases because indirect comparisons suggest longer PFS and higher response rates. There is no head-to-head trial.
• DECISION eligibility: progression within 14 months; RAI-refractory by any of — a target lesion without iodine uptake (68% of patients); uptake with progression within 16 months of RAI (12%); progression after each of two RAI treatments given within 16 months (7%); cumulative ≥600 mCi (34%) (US label).
• Timing: as for any MKI, start promptly for symptomatic disease; asymptomatic, stable or slowly progressive disease can be monitored on TSH suppression (ATA 2025).
• After sorafenib: lenvatinib remains active after one prior MKI (SELECT: PFS 15.1 months in this subgroup), and cabozantinib is the recommended second-line drug without an actionable driver (COSMIC-311; ATA 2025).

Contraindications

• Known severe hypersensitivity to sorafenib (US label). Combination with carboplatin and paclitaxel in squamous cell lung cancer is also contraindicated (US label; not relevant to DTC).
• Relative: unstable coronary disease or recent myocardial infarction (excluded from trials), uncontrolled hypertension, bleeding tendency, recent GI perforation, tumour invading the airway, oesophagus or great vessels (US label; ATA 2025).
• Surgery: withhold for at least 10 days before elective surgery; do not give for at least 2 weeks after major surgery and until the wound has healed (US label).
• Pregnancy and breastfeeding (see below).

• Hand–foot skin reaction, grade 2 (painful erythema and swelling affecting normal activity), DTC column of the label: first occurrence — reduce to 600 mg daily; if no better in 7 days, or on a second or third occurrence — interrupt until grade ≤1, then resume 1 dose level lower (second occurrence) or 2 levels lower (third); fourth occurrence — stop.
• Hand–foot skin reaction, grade 3 (moist desquamation, ulceration, blistering or severe pain stopping work or daily activities): first occurrence — interrupt until grade ≤1, resume 1 level lower; second — interrupt, resume 2 levels lower; third — stop.
• Re-escalation: after grade 2–3 skin toxicity has stayed at grade 0–1 for at least 28 days on a reduced dose, the dose may go up by one level. About half of patients meet this and about half of those tolerate it (US label).
• Other non-haematological toxicity (US label): grade 2 — continue one level lower; grade 3 — interrupt until ≤ grade 2, resume 1 level lower (2 levels if no improvement within 7 days or on a second or third occurrence; 3 levels for DTC on a fourth); grade 4 — stop. If there is no recovery after a 30-day interruption, stop unless the patient is benefiting.
• Cardiovascular and other holds (US label): hypertension — interrupt for symptomatic or persistent grade 2 or grade 3 until diastolic <90 mmHg, then resume one level lower; stop for grade 4. Stop for grade ≥2 cardiac ischaemia, grade 4 heart failure (interrupt grade 3), bleeding needing intervention, any GI perforation, or drug-induced liver injury. For QTc >500 ms or a rise ≥60 ms, interrupt and correct magnesium, potassium and calcium.
• Monitoring: blood pressure weekly for the first 6 weeks, then as needed; TSH monthly (US label). Review at baseline, at least every 2 weeks for 2 months, then every 1–2 months (ATA 2025).

• Hand–foot skin reaction: 69% in DECISION (grade 3–4 19%) by the label count; it usually appears in the first 6 weeks and led 5.3% of DTC patients to stop (US label). Painful, hyperkeratotic lesions and blisters on the palms and soles.
• Preventing hand–foot reaction (ATA 2025): remove calluses before starting and during treatment; keep hands moisturised with fragrance- and alcohol-free products and feet dry; avoid sun and extreme heat or cold; wear cushioned shoes. A 10% urea cream helps prevention; use 20–40% urea on affected areas; consider podiatry. Severe cases may need topical or systemic steroids, antibiotics and analgesia.
• Diarrhoea (68% all grades, 6% grade 3–4 in DECISION): diet changes, fluids, loperamide, then diphenoxylate/atropine (US label; ATA 2025).
• Alopecia (67%) and rash (35%): usually grade 1–2 (US label).
• Hypertension: 40.6% vs 12.4% with placebo; usually mild to moderate and early (US label).
• Thyroid: TSH rose above 0.5 mU/L in 41% vs 16%; check TSH monthly and adjust levothyroxine (US label).
• Hypocalcaemia is more frequent and more severe in DTC than in other cancers; monitor calcium (US label).
• Cardiac and bleeding: cardiac ischaemia or infarction 1.9% vs 0%; bleeding 17.4% in DECISION (US label).
• Weight loss tends to increase over time and needs dietary support (Worden 2015; ATA 2025).
• Other: QT prolongation, drug-induced liver injury, GI perforation and impaired wound healing (US label).

• No radiation precautions apply.
• Women of reproductive potential should use effective contraception during treatment and for 6 months after the last dose; men with female partners of reproductive potential for 3 months (US label).
• Do not breastfeed during treatment and for 2 weeks after the last dose (US label).