Multi-Targeted TKI (VEGFR2, MET, AXL, RET)
Pregnancy: Contraindicated — embryotoxic; effective contraception required during and for 4 months after treatment
Cabozantinib
Brand names: Cabometyx, Cometriq
Adult dose
Dose: RCC first-line: 60 mg once daily; RCC second-line: 60 mg once daily; with nivolumab (CheckMate 9ER): 40 mg once daily
Route: Oral
Frequency: Once daily (fasting — no food 2 hours before or 1 hour after)
Max: 60 mg/day
mRCC — first-line or after VEGFR-TKI; hepatocellular carcinoma (CELESTIAL); MTC (Cometriq brand); cabozantinib's additional MET/AXL inhibition overcomes VEGFR TKI resistance mechanisms
Paediatric dose
Dose: Not established for urology indications N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Not licensed for paediatric RCC
Dose adjustments
Renal
No dose adjustment for mild-moderate renal impairment
Hepatic
Mild: no adjustment; moderate: reduce to 40 mg; severe: avoid
Paediatric weight-based calculator
Not licensed for paediatric RCC
Clinical pearls
- CABOSUN trial (Choueiri et al. NEJM 2016): cabozantinib significantly improved PFS vs sunitinib in intermediate/poor-risk mRCC (8.6 vs 5.3 months); METEOR trial (NEJM 2015): cabozantinib superior to everolimus after VEGFR-TKI — established cabozantinib across first and second line
- MET and AXL inhibition: key mechanism distinguishing cabozantinib from sunitinib/pazopanib — MET and AXL are upregulated as resistance mechanisms to VEGFR TKIs; cabozantinib simultaneously blocks these escape pathways, explaining superior post-VEGFR-TKI efficacy
- CheckMate 9ER: cabozantinib 40 mg + nivolumab significantly improved OS vs sunitinib in first-line mRCC — combination immunotherapy-TKI is now the preferred first-line approach for intermediate/poor-risk mRCC; NICE TA661
- GI perforations and fistulae: serious but rare complication — hold cabozantinib if abdominal pain/ileus; permanently discontinue if perforation confirmed; particular risk in patients with prior GI surgery or radiation
- Fasting requirement: cabozantinib absorption significantly affected by food — must be taken on empty stomach; clinically meaningful effect on drug levels if taken with high-fat meal
Contraindications
- Uncontrolled hypertension
- Recent (within 6 months) arterial thromboembolic event
- Known hypersensitivity
Side effects
- Diarrhoea (most common)
- Fatigue
- Hand-foot syndrome
- Hypertension
- Nausea
- Decreased appetite
- Hepatotoxicity
- Fistulae/GI perforations (rare but serious)
- Hypothyroidism
- Thromboembolism
Interactions
- Strong CYP3A4 inhibitors — increase cabozantinib; reduce to 40 mg
- Strong CYP3A4 inducers — reduce cabozantinib; increase to 80 mg
- Anticoagulants — increased bleeding risk
Monitoring
- Blood pressure (weekly initially)
- LFTs (each cycle)
- FBC
- TFTs (every 2 months)
- Diarrhoea/stool frequency (each visit)
- Hand-foot syndrome grading
- Abdominal symptoms (fistula/perforation)
Reference: BNFc; BNF 90; CABOSUN trial (Choueiri et al. NEJM 2016); METEOR trial (Choueiri et al. NEJM 2015); CheckMate 9ER (Choueiri et al. NEJM 2021); NICE TA661; MHRA SPC Cabometyx. Verify against your local formulary and the latest BNF before prescribing.
Related
Curated clinical cross-links plus same-class fallbacks.
Calculators