Generic (Cabozantinib) CABODX 80

Cabozantinib is an anti-cancer medication used to treat medullary thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma. It is a small molecule inhibitor of the tyrosine kinases c-Met and VEGFR2, and also inhibits AXL and RET.

Medullary Thyroid Cancer

Capsule only

Indicated for treatment of progressive, metastatic medullary thyroid cancer (MTC)

140 mg PO qDay

Continue until disease progression or unacceptable toxicity occurs

Renal Cell Carcinoma

Tablet only

Combination with nivolumab

• Indicated in combination with nivolumab for first-line treatment of advanced renal cell carcinoma (RCC)
• Cabozantinib 40 mg PO qDay PLUS nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity
• Nivolumab only: Continue for up to 2 years

Single agent

• Indicated for advanced RC
• 60 mg PO qDay
• Continue until disease progression or unacceptable toxicity occurs

Hepatocellular Carcinoma

Tablet only

Indicated for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib

60 mg PO qDay

Continue until disease progression or unacceptable toxicity occurs

Differentiated Thyroid Cancer

Indicated for locally advanced or metastatic differentiated thyroid cancer (DTC) in adults who have progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible

BSA >1.2 m²: 60 mg PO qDay

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dosage reductions (Cabometyx)

• Monotherapy with BSA >1.2 m2

  • First dose reduction: 40 mg PO qDay
  • Second dose reduction: 20 mg PO qDay
  • Previously receiving 20 mg qDay: Resume at same dose
  • Unable to tolerate 20 mg qDay: Discontinue treatment

• In combination with nivolumab

  • First dose reduction: 20 mg PO qDay
  • Second dose reduction: 20 mg PO every other day
  • Previously receiving 20 mg every other day: Resume at same dose
  • Unable to tolerate 20 mg every other day: Discontinue treatment

Withhold dose until Grade ≤1 or until complete resolution

• Resume at reduced dose
• Grade ≥2 diarrhea
• Grade 3 or intolerable grade 2 palmar-plantar erythrodysesthesia
• Grade 2 or 3 proteinuria
• Any grade osteonecrosis of jaw (ONJ)
• Grade ≥3 or intolerable grade 2 other adverse reactions

Withhold dose until Grade ≤1

• Tablet

  • Consider corticosteroid therapy if withheld or discontinued when administered in combination with nivolumab
  • ALT or AST >3x ULN but ≤10x ULN with concurrent total bilirubin [TB] <2x ULN
  • After recovery, consider rechallenge with one or both of Cabometyx and nivolumab
  • If rechallenging with nivolumab with or without Cabometyx, refer to nivolumab prescribing information

Withhold dose until adequately controlled at Grade ≤2

• Resume at reduced dose
• Grade 3 hypertension and hypertensive crisis

Permanently discontinue

• Grades 3 or 4 hemorrhage
• Any grade gastrointestinal perforation
• Grade 4 fistula
• Any grade acute myocardial infarction
• Grade ≥2 cerebral infarction
• Grade 3 or 4 arterial thromboembolic events
• Grade 4 venous thromboembolic events
• Grade 4 hypertension or uncontrolled hypertensive crisis
• Nephrotic syndrome
• Reversible posterior leukoencephalopathy syndrome (RPLS)
• ALT or AST >10x ULN or >3x ULN with concurrent TB ≥2x ULN; permanently discontinue both nivolumab and Cabometyx

CYP3A4 inhibitors

• Avoid coadministration with strong CYP3A4 inhibitors
• Cometriq: If strong CYP3A4 inhibitor required, decrease cabozantinib dose by 40 mg/day (eg, from 140 mg to 100 mg qDay)
• Cabometyx: If strong CYP3A4 inhibitor required, decrease cabozantinib dose by 20 mg/day (eg, from 60 mg to 40 mg qDay)
• Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued

CYP3A4 inducers

• Avoid coadministration of strong CYP3A4 inducers
• Cometriq: If strong CYP3A4 inducer required, increase dose by 40 mg/day (eg, from 140 mg to 180 mg qDay); do not exceed 180 mg/day
• Cabometyx: If strong CYP3A4 inducer required, increase dose by 20 mg/day (eg, from 60 mg to 80 mg qDay); do not exceed 80 mg/day
• Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued

Hepatic impairment

• Tablet

  • Mild-to-moderate (Child-Pugh A or B): Reduce starting dose to 80 mg/day
  • Moderate (Child-Pugh C): Not recommended

• Tablet

  • Mild (Child-Pugh A): No dosage adjustment necessary
  • Moderate (Child-Pugh B): Reduce starting dose to 40 mg/day
  • Severe (Child-Pugh C): Avoid use

Renal impairment

• Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment necessary
• Severe (CrCl <30 mL/min): No experience