Sorafenib — Drug Monograph

Brand names: Nexavar

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Oral multikinase inhibitor with dual anti-proliferative and anti-angiogenic activity. Inhibits RAF kinases (BRAF and CRAF), blocking the MAPK/ERK pathway, and simultaneously inhibits VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-β, KIT, FLT3, and RET, disrupting tumor angiogenesis and stromal signaling.

FDA Indications

• Advanced renal cell carcinoma (RCC) — FDA approved December 2005 (TARGET trial: PFS HR 0.44)
• Unresectable hepatocellular carcinoma (HCC) — FDA approved November 2008 (SHARP trial: OS HR 0.69)
• Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAI) — FDA approved November 2013

Common Side Effects

• Hand-foot skin reaction (HFSR/palmar-plantar erythrodysesthesia) — dose-limiting; blistering and hyperkeratosis at pressure points
• Diarrhea
• Hypertension
• Fatigue
• Alopecia
• Rash/desquamation
• Nausea
• Anorexia
• Weight loss

Clinical Pearl

HFSR is the most distinctive and dose-limiting toxicity of sorafenib. Unlike chemotherapy-induced hand-foot syndrome (diffuse erythema), sorafenib causes hyperkeratotic, blister-forming lesions at pressure points. Preventive measures include thick urea cream (20–40%), cushioned footwear, and avoidance of friction. Early dose reduction at Grade 2 prevents Grade 3 events. HFSR is more common with sorafenib than sunitinib due to PDGFR-β inhibition in pericytes.

Related Therapies & Mechanisms

• Cabozantinib (Cabometyx) — Tyrosine Kinase Inhibitor · HCC
• Lenvatinib (Lenvima) — Tyrosine Kinase Inhibitor · HCC
• Axitinib (Inlyta) — Tyrosine Kinase Inhibitor · RCC
• Dabrafenib (Tafinlar) — Tyrosine Kinase Inhibitor · Thyroid