Class: Oral multikinase inhibitor (VEGFR-TKI)
Mechanism of Action
- Inhibits multiple receptor tyrosine kinases:
- VEGFR1–3 → ↓ angiogenesis
- FGFR1–4, PDGFRα, KIT, RET → antitumor activity
Approved Indications
- Differentiated thyroid cancer (DTC):
- Locally recurrent or metastatic, radioiodine-refractory
- Renal cell carcinoma (RCC):
- In combination with everolimus after one prior anti-angiogenic therapy
- Hepatocellular carcinoma (HCC):
- First-line for unresectable disease (alternative to sorafenib)
- Endometrial carcinoma:
- In combination with pembrolizumab, for advanced endometrial carcinoma (non-MSI-H, mismatch repair–proficient) after prior systemic therapy
Dosing (Adults)
- Differentiated thyroid cancer: 24 mg PO once daily
- RCC: 18 mg PO once daily + everolimus 5 mg PO daily
- HCC:
- ≥60 kg: 12 mg PO once daily
- <60 kg: 8 mg PO once daily
- Endometrial cancer (with pembrolizumab): 20 mg PO once daily
(Swallow capsules whole, with or without food. Can disperse in water if needed.)
Toxicities & Monitoring
Common:
- Hypertension (very common, dose-limiting)
- Proteinuria
- Diarrhea, nausea, decreased appetite, weight loss
- Fatigue, stomatitis, hand–foot syndrome
- Hypothyroidism (especially in thyroid cancer patients)
Serious:
- Arterial thromboembolic events (MI, stroke)
- QT prolongation
- Hepatotoxicity
- Renal impairment / nephrotic syndrome
- GI perforation, fistula
- Hemorrhage
Monitoring:
- BP (baseline and regularly)
- Urine protein (baseline, q2w initially, then monthly)
- ECG, electrolytes if QT risk
- Liver and renal function tests
- TSH (in thyroid cancer patients)
Drug Interactions
- Substrate of CYP3A4 and P-gp, but clinically significant interactions are limited.
- Avoid strong CYP3A4 inducers if possible.
- Additive toxicity with other antihypertensives, anticoagulants, QT-prolonging drugs.
Clinical Pearls for Oncology Pharmacist
- Hypertension often develops within 2 weeks of starting → initiate or optimize antihypertensives.
- Dose reductions common: from 24 → 20 → 14 → 10 mg daily.
- Not interchangeable with sorafenib or vandetanib; lenvatinib has broader FGFR activity.
- In HCC, weight-based dosing is crucial.
- Watch for combination toxicities with everolimus (stomatitis, cytopenias, renal dysfunction).