Cabozantinib (Cometriq)

Note: Cometriq is the brand name for cabozantinib's medullary thyroid cancer indication. Cabometyx is the brand name for cabozantinib's renal cell carcinoma indication.

General information

Class/mechanism: Tyrosine kinase inhibitor; inhibits RET, MET/c-Met, VEGFR-1, VEGFR-2, VEGFR-3, KIT, TRKB, FLT-3, AXL, and TIE-2.
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias or the prescribing information.

Diseases for which it is established (work in progress)

• Hepatocellular carcinoma
• Medullary thyroid cancer
• Renal cell carcinoma
  • Clear cell renal cell carcinoma
  • Papillary renal cell carcinoma
• Thyroid cancer, differentiated

Diseases for which it is used

• Gastrointestinal stromal tumor
• Non-small cell lung cancer
• Osteosarcoma
• Prostate cancer
• Thyroid cancer

Patient drug information

• Cabozantinib (Cometriq) package insert pages 20-24 (the numbering for the PDF is off, so in some PDF viewers, the patient information is on pages 27-31)
• Cabozantinib (Cabometyx) package insert
• Cabozantinib (Cometriq) patient drug information (Chemocare)
• Cabozantinib (Cometriq) patient drug information (UpToDate)

History of changes in FDA indication

Thyroid cancer, differentiated

• 2021-09-17: Approved for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are ineligible or refractory to radioactive iodine. (Based on COSMIC-311)

Hepatocellular carcinoma

• 2019-01-14: Approved for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. (New disease entity; based on CELESTIAL)

Medullary thyroid cancer

• 2012-11-29: Initial approval (as Cometriq) for treatment of progressive metastatic medullary thyroid cancer (MTC). (Based on EXAM)

Renal cell carcinoma

• 2016-04-25: Approved (as Cabometyx) for the treatment of advanced renal cell carcinoma in patients who have received prior anti-angiogenic therapy. (New disease entity; based on METEOR)
• 2017-12-19: Granted FDA regular approval for treatment of patients with advanced renal cell carcinoma (RCC). (Converted to regular approval; no longer requires prior treatment; based on CABOSUN)

History of changes in EMA indication

• 2014-03-21: Initial authorization as Cometriq. Cometriq is indicated for the treatment of adult patients with progressive, unresectable locally advanced or metastatic medullary thyroid carcinoma. (Based on EXAM)
• 2016-09-09: Initial authorization as Cabometyx. Cabometyx is indicated for the treatment of advanced renal cell carcinoma (RCC) in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy. (Based on METEOR)
• 2018-05-08: Extension of indication to include for the treatment of advanced renal cell carcinoma the ‘treatment-naïve adults with intermediate or poor risk’ for CABOMETYX.
• 2018-11-12: Extension of indication to add Cabometyx as monotherapy for the treatment of hepatocellular carcinoma in adults who have previously been treated with sorafenib.
• 2021-03-26: Extension of indication to include in combination with nivolumab first line treatment of advanced renal cell carcinoma for CABOMETYX.
• 2022-04-29: Extension of indication to include monotherapy treatment of adults and adolescent patients aged 12 years and older, with locally advanced or metastatic differentiated thyroid carcinoma (DTC), refractory to radioactive iodine (RAI) who have progressed during or after prior systemic therapy for CABOMETYX.
• 2022-04-29: Extension of indication to include monotherapy treatment of adults and adolescent patients aged 12 years and older, with locally advanced or metastatic differentiated thyroid carcinoma (DTC), not eligible for radioactive iodine (RAI) who have progressed during or after prior systemic therapy for CABOMETYX.

History of changes in Health Canada indication

• 2018-09-14: Initial notice of compliance for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior vascular endothelial growth factor (VEGF)-targeted therapy.
• 2019-10-10: New indication
• 2019-11-08: New indication
• 2021-10-12: New indication
• 2022-04-28: New indication

History of changes in PMDA indication

• 2020-03-25: Initial approval for the treatment of unresectable or metastatic renal cell carcinoma.
• 2020-11-27: New indication for the treatment of unresectable hepatocellular carcinoma that has progressed after cancer chemotherapy.

Also known as

• Code names: XL-184
• Brand names: Cabanib, Cabdual, Cabolong, Cabonrom, Cabotib, Cabotres, Caboxen, Caboxib, Cabozanib, Cabozanix, Cabozat, CabzoRed, Cabometyx, Cazanat, Comarit, Cometriq, Kabonib, Lucicaboz, Lupizotib