Cabometyx

Advanced renal cell carcinoma (RCC) — as monotherapy or in combination with nivolumab (first-line); Hepatocellular carcinoma (HCC) previously treated with sorafenib; Locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible

RCC (monotherapy): 60 mg orally once daily
RCC (with nivolumab): 40 mg orally once daily
HCC: 60 mg orally once daily
DTC: 60 mg orally once daily
Take on empty stomach — do not eat for at least 2 hours before and 1 hour after
Dose reductions: 40 mg, then 20 mg

Tablets: 20 mg, 40 mg, 60 mg

None listed.

• Hemorrhage: Severe and fatal hemorrhages reported (including GI and pulmonary). Do not administer if recent history of hemorrhage or hemoptysis.
• GI Perforations and Fistulas: Monitor for symptoms. Discontinue for perforations or Grade 4 fistulas.
• Thrombotic Events: Venous and arterial thromboembolic events reported.
• Hypertension and Hypertensive Crisis: Monitor BP before initiation and regularly during treatment.
• Diarrhea: Grade 3 in up to 16%. Manage promptly with standard antidiarrheal treatments.
• Palmar-Plantar Erythrodysesthesia (PPE): Hand-foot syndrome reported in up to 45% of patients.
• Hepatotoxicity: Monitor liver function tests before and during treatment.
• Wound Complications: Withhold for at least 3 weeks prior to elective surgery.
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
• Embryo-Fetal Toxicity

Diarrhea (63%), fatigue (56%), PPE/hand-foot syndrome (45%), decreased appetite (46%), hypertension (37%), nausea (35%), vomiting (24%), weight decreased (24%), dysgeusia (19%), stomatitis (22%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Cabozantinib is an inhibitor of multiple receptor tyrosine kinases including VEGF receptors (VEGFR1, VEGFR2, VEGFR3), MET (hepatocyte growth factor receptor), AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT3, and TIE-2. These receptor tyrosine kinases are involved in tumor angiogenesis, invasion, metastasis, and tumor microenvironment modulation.

Tmax: 2-5 hours. Half-life: approximately 99 hours. Protein binding: ≥99.7%. Metabolized primarily by CYP3A4. Fecal excretion (54%), urinary excretion (27%).

Clinical efficacy and safety data supporting the approval of Cabometyx are available in the full prescribing information and from the pivotal clinical trials listed below.

• METEOR (RCC, 2nd-line) — Cabozantinib vs. everolimus in advanced RCC after prior VEGFR-targeted therapy. Phase III, n=658.
  🔬 NCT01865747 ↗ 📄 Primary Publication ↗ 📄 Primary Publication ↗
• CABOSUN (RCC, 1st-line) — Cabozantinib vs. sunitinib as initial therapy for intermediate/poor-risk mRCC. Phase II (Alliance A031203), n=157.
  🔬 NCT01835158 ↗ 📄 Primary Publication ↗ 📄 Primary Publication ↗
• CheckMate 9ER (RCC, 1st-line combo) — Nivolumab + cabozantinib vs. sunitinib for previously untreated advanced RCC. Phase III, n=651.
  🔬 NCT03141177 ↗ 📄 Primary Publication ↗
• CELESTIAL (HCC, 2nd-line) — Cabozantinib vs. placebo in previously treated advanced HCC. Phase III, n=707.
  🔬 NCT01908426 ↗ 📄 Primary Publication ↗

Cabometyx has FDA-approved indications across the following cancer types covered on PipelineEvidence: