Generic (Selpercatinib) SEPADX

The targeted drug selpercatinib  has been a treatment option for some people with lung cancer or thyroid cancer whose tumors contain specific changes in a gene called RET.

Non-small Cell Lung Cancer

Indicated for metastatic RET fusion-positive non-small cell lung cancer (NSCLC)

<50 kg: 120 mg PO BID

≥50 kg: 160 mg PO BID

Continue until disease progression or unacceptable toxicity

Medullary Thyroid Cancer

Indicated for advanced or metastatic RET-mutant medullary thyroid cancer (MTC) in patients who required systemic therapy

<50 kg: 120 mg PO BID

≥50 kg: 160 mg PO BID

Continue until disease progression or unacceptable toxicity

Thyroid Cancer

Indicated for advanced or metastatic RET fusion-positive thyroid cancer in patients who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)

<50 kg: 120 mg PO BID

≥50 kg: 160 mg PO BID

Continue until disease progression or unacceptable toxicity

Other RET Fusion-Positive Solid Tumors

Indicated for locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options

<50 kg: 120 mg PO BID

≥50 kg: 160 mg PO BID

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dose reduction recommendations

• Weight <50 kg

  • First reduction: 80 mg BID
  • Second reduction: 40 mg BID
  • Third reduction: 40 mg qDay
  • Permanently discontinue if unable to tolerate third dose reduction

• Weight ≥50 kg

  • First reduction: 120 mg BID
  • Second reduction: 80 mg BID
  • Third reduction: 40 mg BID
  • Permanently discontinue if unable to tolerate third dose reduction

Hepatotoxicity grade 3 or 4

• Withhold dosing and monitor AST/ALT once weekly until resolution to Grade 1 or baseline
• Resume at reduced dose by 2 dose levels and monitor AST/ALT once weekly until 4 weeks after reaching dose taken prior to the onset of Grade 3 or 4 increased AST or ALT
• Increase dose by 1 dose level after a minimum of 2 weeks without recurrence, and then increase to dose taken before Grade 3 or 4 increased AST or ALT after minimum of 4 weeks without recurrence

Interstitial lung disease/ pneumonitis

• Grade 2: Withhold until resolution; resume at a reduced dose; discontinue for recurrent ILD/pneumonitis
• Grade 3 or 4: Discontinue for confirmed ILD/pneumonitis

Hypothyroidism

• Grade 3 or 4: Withhold until resolution to Grade 1 or baseline; discontinue based on severity

Hypertension

• Grade 3: Withhold dosing for Grade 3 hypertension that persists despite optimal antihypertensive therapy; resume at reduced dose when hypertension controlled
• Grade 4: Discontinue

QT prolongation

• Grade 3: Withhold dosing until recovery to baseline or Grade ≤1; resume at reduced dose
• Grade 4: Discontinue

Hemorrhagic events grade 3 or 4

• Withhold dosing until recovery to baseline or Grade ≤1
• Discontinue for severe or life-threatening hemorrhagic events

Hypersensitivity reactions all grades

• Withhold dosing until resolution; initiate corticosteroids
• Resume at reduced dose by 3 dose levels while continuing corticosteroids
• Increase dose by 1 dose level each week until the dose taken prior to hypersensitivity event is reached, then taper corticosteroids

Other adverse effects grade 3 or 4

• Withhold dosing until recovery to baseline or Grade ≤1
• Resume at reduced dose

Coadministration with CYP3A inhibitors

• Avoid coadministration; if unable to avoid, reduce selpercatinib dose
• After inhibitor has been discontinued for 3-5 elimination half-lives, resume selpercatinib at dose take prior to initiated the CYP3A inhibitor

• Moderate CYP3A inhibitor

  • If current dose is 120 mg BID, reduce to 80 mg BID
  • If current dose is 160 mg BID, reduce to 120 mg BID

• Strong CYP3A inhibitor

  • If current dose is 120 mg BID, reduce to 40 mg BID
  • If current dose is 160 mg BID, reduce to 80 mg BID

Renal impairment

• Mild-to-severe (CrCl ≥15 mL/min): No dose adjustment required
• ESRD: Recommended dose not established

Hepatic impairment

• Mild or moderate

  • No dose adjustment required
  • Mild defined as: TB ≤ULN with AST >ULN OR TB >1-1.5x ULN with any AST
  • Moderate defined as: TB >1.5-3x ULN with any AST

• Severe

  • If current dose is 120 mg or 160 mg BID, reduce to 80 mg BID
  • Severe defined as: Total biliruvin (TB) >3-10x ULN with any AST

Acid-reducing agents

Avoid with PPIs, histamine-2 (H2) receptor antagonists, or locally acting antacids

• If unable to avoid

  • PPIs: Take with food when coadministered
  • H2 receptor antagonist: Take selpercatinib 2 hr before or 10 hr after an H2 antagonist
  • Locally acting antacid: Take selpercatinib 2 hr before or 2 hr after antacid

Dosing Considerations

Select patients for treatment based on presence of RET gene fusion (NSCLC or thyroid cancer) or specific RET gene mutation (MTC) in tumor specimens or plasma