LuciVora (Vorasidenib)

About Vorasidenib

Vorasidenib is an oral, brain-penetrant, dual inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) enzymes, approved for treating grade 2 IDH-mutant astrocytoma or oligodendroglioma in adults and children 12 years and older, following surgery. 

Adult

Astrocytoma or Oligodendroglioma

Indicated for Grade 2 astrocytoma or oligodendroglioma with susceptible isocitrate dehydrogenase (IDH)-1 or IDH-2 mutation following surgery including biopsy, sub-total resection, or gross total resection

40 mg PO qDay until disease progression or unacceptable toxicity

Dosage Modifications

Recommended dosage reductions

• First reduction: 20 mg PO qDay
• Second reduction: 10 mg PO qDay
• Permanently discontinue if second dosage reduction not tolerated

Hepatotoxicity

• ALT or AST >ULN to 3 x ULN without concurrent total bilirubin >2 x ULN

  • Continue current dose
  • Monitor liver function tests (LFTs) weekly until recovery to

• ALT or AST >3-5 x ULN without concurrent total bilirubin >2 x ULN

  • Hold until recovery to ≤Grade 1 or baseline
  • Resume at same dose for recovery ≤28 days or at reduced dose for recovery >28 days
  • Recurrence: Hold therapy until recovery to ≤Grade 1 or baseline and resume at reduced dose

• ALT or AST >5-20 x ULN without concurrent total bilirubin >2 x ULN

  • Hold therapy until recovery to ≤Grade 1 or baseline
  • Resume at reduced dose for recovery ≤28 days or permanently discontinue for recovery >28 days
  • Recurrence: Permanently discontinue

• ALT or AST >3-20 x ULN with concurrent total bilirubin >2 x ULN

  • Hold therapy until recovery to ≤Grade 1 or baseline
  • Resume at reduced dose
  • Recurrence: Permanently discontinue

• Any ALT or AST >20 x ULN

  • Permanently discontinue

Other adverse reactions

• Grade 3

  • Hold therapy until recovery to ≤Grade 1 or baseline
  • Resume at reduced dose
  • Recurrence: Permanently discontinue

• Grade 4

  • Permanently discontinue

Renal impairment

• CrCl >40 mL/min: No dosage adjustment necessary
• CrCl ≤40 mL/min or on dialysis: Not studied; monitor for adverse reactions and adjust dose as recommended

Hepatic impairment

• Mild or moderate (Child-Pugh class A or B): No dosage adjustment necessary
• Severe (Child-Pugh class C): Not studied; monitor for adverse reactions and adjust dose as recommended

Dosing Considerations

Evaluate blood chemistry and LFTs before initiating

Patient selection

• Test for presence of IDH1 or IDH2 mutations in tumor specimens

Pediatric

Astrocytoma or Oligodendroglioma

Indicated for Grade 2 astrocytoma or oligodendroglioma with susceptible isocitrate dehydrogenase (IDH)-1 or IDH-2 mutation following surgery including biopsy, sub-total resection, or gross total resection in patients ≥12 years

≥40 kg: 40 mg PO qDay

<40 kg: 20 mg PO qDay

Continue until disease progression or unacceptable toxicity

Safety and efficacy not established in patients <12 years

Dosage Modifications

Recommended dosage adjustments

• ≥40 kg

  • First reduction: 20 mg PO qDay
  • Second reduction: 10 mg PO qDay

• <40 kg

  • First reduction: 10 mg PO qDay
  • Permanently discontinue if reduced dose not tolerated

Hepatotoxicity

• ALT or AST >ULN to 3 x ULN without concurrent total bilirubin >2 x ULN

  • Continue current dose
  • Monitor liver function tests (LFTs) weekly until recovery to

• ALT or AST >3-5 x ULN without concurrent total bilirubin >2 x ULN

  • Hold until recovery to ≤Grade 1 or baseline
  • Resume at same dose for recovery ≤28 days or at reduced dose for recovery >28 days
  • Recurrence: Hold therapy until recovery to ≤Grade 1 or baseline and resume at reduced dose

• ALT or AST >5-20 x ULN without concurrent total bilirubin >2 x ULN

  • Hold therapy until recovery to ≤Grade 1 or baseline
  • Resume at reduced dose for recovery ≤28 days or permanently discontinue for recovery >28 days
  • Recurrence: Permanently discontinue

• ALT or AST >3-20 x ULN with concurrent total bilirubin >2 x ULN

  • Hold therapy until recovery to ≤Grade 1 or baseline
  • Resume at reduced dose
  • Recurrence: Permanently discontinue

• Any ALT or AST >20 x ULN

  • Permanently discontinue

Other adverse reactions

• Grade 3

  • Hold therapy until recovery to ≤Grade 1 or baseline
  • Resume at reduced dose
  • Recurrence: Permanently discontinue

• Grade 4

  • Permanently discontinue

Renal impairment

• CrCl >40 mL/min: No dosage adjustment necessary
• CrCl ≤40 mL/min or on dialysis: Not studied; monitor for adverse reactions and adjust dose as recommended

Hepatic impairment

• Mild or moderate (Child-Pugh class A or B): No dosage adjustment necessary
• Severe (Child-Pugh class C): Not studied; monitor for adverse reactions and adjust dose as recommended

Dosing Considerations

Evaluate blood chemistry and LFTs before initiating

Patient selection

• Test for presence of IDH1 or IDH2 mutations in tumor specimens