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Introduction

Cabozantinib is a targeted therapy approved for the treatment of advanced cancers. As a tyrosine kinase inhibitor (TKI), it blocks multiple receptors involved in tumor growth, angiogenesis, and metastasis. Below is an overview of its primary uses, mechanisms, and clinical relevance.

FDA-Approved Indications

Cabozantinib is primarily used for:

• Renal Cell Carcinoma (RCC)

First-line treatment for advanced RCC in combination with nivolumab.

Monotherapy for previously treated RCC.

• Differentiated Thyroid Cancer (DTC)

Treats medullary thyroid cancer (MTC) and radioactive iodine-refractory DTC.

• Hepatocellular Carcinoma (HCC)

Second-line therapy for HCC after sorafenib failure.

Off-Label and Investigational Uses

Beyond FDA approvals, cabozantinib shows promise in:

• Non-Small Cell Lung Cancer (NSCLC)

MET exon 14 skipping mutations or RET fusions.

• Prostate Cancer

mCRPC with bone metastases (combination with androgen deprivation therapy).

• Glioblastoma

Clinical trials exploring efficacy in recurrent cases.

Mechanism of Action

Target Receptors	Biological Effects
MET, VEGFR2	Inhibits tumor angiogenesis
AXL, RET	Suppresses tumor invasion
ROS1. NTRK	Blocks growth signaling

By dual targeting of vascular and oncogenic pathways, cabozantinib disrupts tumor microenvironment and metastatic potential.

Dosage and Administration

Standard Dose: 60 mg orally once daily (with or without food).

Adjustments: Reduced to 40 mg or 20 mg for severe adverse effects.

Key Side Effects

Common toxicities include:

• Gastrointestinal: Diarrhea, nausea, stomatitis.
• Dermatologic: Hand-foot syndrome, rash.
• Cardiovascular: Hypertension, thrombosis.
• Hepatic: Elevated liver enzymes.

Patient Selection and Monitoring

• Biomarker Testing: MET, RET, or VEGFR alterations guide eligibility.
• Regular Checkups: Monitor blood pressure, liver function, and proteinuria.

Conclusion

Cabozantinib represents a versatile tool in precision oncology, particularly for tumors harboring specific genetic alterations. Ongoing trials may expand its role in cancers like NSCLC and glioblastoma, underscoring its potential to reshape treatment paradigms.

Table: Cabozantinib in Clinical Practice

Cancer Type	Line of Therapy	Key Trials	Biomarkers
RCC	First/Second	CheckMate 9ER	—
DTC	Advanced	COSMIC-311	RET/MTC
HCC	Second	CELESTIAL	—
NSCLC	Second+	GEOMETRY	MET exo14