Vandetanib — Drug Monograph

Brand names: Caprelsa

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Multi-kinase inhibitor targeting RET, VEGFR2 (KDR), VEGFR3, and EGFR (ErbB1). In medullary thyroid cancer (MTC), activating RET germline mutations (C634W/F/R/Y in MEN2A; M918T in MEN2B) and somatic mutations drive constitutive RET kinase activity, promoting thyroid C-cell proliferation. Vandetanib inhibits mutant RET, suppressing MAPK and PI3K/AKT signaling. Concurrent VEGFR2/3 inhibition exerts antiangiogenic effects, reducing tumor vascularization. EGFR inhibition provides additional anti-proliferative activity. Unlike the more selective RET inhibitors selpercatinib and pralsetinib,…

FDA Indications

• Symptomatic or progressive medullary thyroid cancer (MTC) — unresectable locally advanced or metastatic, in adults (FDA approved April 2011 — ZETA Phase 3 trial: PFS HR 0.46, median PFS 30.5 vs 19.3 months vs placebo)

Common Side Effects

• Diarrhea / colitis (57%)
• Rash / photosensitivity dermatitis (45%)
• Nausea (33%)
• Hypertension (33%)
• Headache (26%)
• Fatigue (24%)
• QTc prolongation (14–36%)
• Decreased appetite
• Abdominal pain
• Corneal opacity / keratopathy (slit-lamp deposits)

Clinical Pearl

Vandetanib was the first approved systemic therapy for progressive MTC but is now largely supplanted in RET-mutant MTC by the highly selective RET inhibitors selpercatinib and pralsetinib, which achieve higher ORRs (~70%) with far better tolerability. Vandetanib may still have a role in RET wild-type MTC or in resource-limited settings. The mandatory CAPRELSA REMS program reflects the QTc prolongation risk; prescribers must be enrolled and patients must be monitored with a standardized…

Related Therapies & Mechanisms

• Cabozantinib (Cabometyx) — Tyrosine Kinase Inhibitor · Thyroid
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• Larotrectinib (Vitrakvi) — Tyrosine Kinase Inhibitor · Thyroid
• Lenvatinib (Lenvima) — Tyrosine Kinase Inhibitor · Thyroid