FAQ

Cabozantinib is a multikinase inhibitor used primarily in the treatment of advanced or metastatic cancers. Its mechanism of action involves targeting multiple tyrosine kinases, including MET, VEGFR1/2/3, RET, ROS1, AXL, NTRK, and KIT, which are implicated in tumor growth, angiogenesis, metastasis, and drug resistance.

1. Renal Cell Carcinoma (RCC)

• Advanced RCC: Approved as a first-line therapy in combination with nivolumab (an immune checkpoint inhibitor) and as a single-agent treatment for previously treated advanced RCC.
  Example: In the CABOSUN trial, cabozantinib demonstrated superior progression-free survival (PFS) and overall survival (OS) compared to sunitinib in intermediate- or poor-risk RCC patients.

2. Hepatocellular Carcinoma (HCC)

• Second-Line Therapy: Indicated for patients with HCC previously treated with sorafenib.
  Example: The CELESTIAL trial showed that cabozantinib extended OS (10.2 months vs. 8.0 months with placebo) and PFS (5.2 months vs. 1.9 months) in sorafenib-refractory HCC.

3. Thyroid Cancer

• Medullary Thyroid Cancer (MTC): Approved for progressive, metastatic MTC.
  Example: In the EXAM trial, cabozantinib significantly improved PFS (11.2 months vs. 4.0 months with placebo).
• Differentiated Thyroid Cancer (DTC): Used for radioactive iodine-refractory DTC after prior VEGFR-targeted therapy.

4. Off-Label/Investigational Uses

• Non-Small Cell Lung Cancer (NSCLC): Studied in RET fusion-positive NSCLC and EGFR wild-type NSCLC, showing efficacy in combination with EGFR TKIs.
• Prostate Cancer: Being investigated for metastatic castration-resistant prostate cancer (mCRPC) with bone metastases.
• Other Solid Tumors: Ongoing trials in osteosarcoma, glioblastoma, and endometrial cancer.

Mechanism of Action

Cabozantinib inhibits:

• MET/AXL: Overcomes resistance to VEGF inhibitors and targets tumor microenvironment.
• VEGFR: Blocks angiogenesis, starving tumors of blood supply.
• RET/ROS1/NTRK: Addresses oncogenic driver mutations in specific tumor types.

Dosing & Administration

• Oral tablet: 60 mg once daily (adjustable for tolerability).
• Food Interaction: Administered on an empty stomach (1 hour before or 2 hours after meals) to enhance absorption.

Safety Profile

• Common Adverse Events: Diarrhea, fatigue, palmar-plantar erythrodysesthesia, hypertension, nausea, and decreased appetite.
• Serious Risks: Hemorrhage, thromboembolic events, gastrointestinal perforations, and reversible posterior leukoencephalopathy syndrome (RPLS).

Drug Interactions

• CYP3A4 Inhibitors/Inducers: Avoid strong CYP3A4 inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin) due to altered cabozantinib plasma levels.
• P-gp Inhibitors: Concomitant use with P-gp inhibitors (e.g., cyclosporine) may increase cabozantinib exposure.

Contraindications & Precautions

• Pregnancy/Lactation: Avoid use due to fetal harm; advise contraception during treatment and for 4 months afterward.
• Hepatic/Renal Impairment: Dose adjustments required for moderate hepatic impairment; avoid in severe hepatic impairment.