TUKADX (Tucatinib)

Tucatinib  is an anticancer medication used for the treatment of HER2-positive breast cancer. It is a small molecule inhibitor of HER2. 

Advanced or Metastatic Breast Cancer

Indicated in combination with trastuzumab and capecitabine for treatment of advanced unresectable or metastatic human epidermal growth factor (HER2)-positive breast cancer (including brain metastases) in patients who have received ≥1 anti-HER2-based regimens in the metastatic setting

300 mg PO BID in combination with trastuzumab and capecitabine

Continue until disease progression or unacceptable toxicity

Refer to the full prescribing information for trastuzumab and capecitabine for additional information

Colorectal Cancer

Indicated in combination with trastuzumab for RAS wild-type HER 2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy

300 mg PO BID

Continue until disease progression or unacceptable toxicity

Refer to the full prescribing information for trastuzumab for additional inforation

Dosage Modifications

Refer to the full prescribing information for trastuzumab and capecitabine for dosage modifications

Dose reductions for adverse reactions

• First reduction: 250 mg PO BID
• Second reduction: 200 mg PO BID
• Third reduction: 150 PO BID
• Unable to tolerate 150 mg PO BID: Permanently discontinue

Diarrhea

• Grade 3 without antidiarrheal treatment: Initiate or intensify appropriate medical therapy; hold until recovery to Grade ≤1, then resume at same dose
• Grade 3 with antidiarrheal therapy: Initiate or intensify appropriate medical therapy; hold until recovery to Grade ≤1, then resume at same dose or at next lower dose
• Grade 4: Permanently discontinue

Hepatotoxicity

• Grade 2 bilirubin (>1.5 to 3x ULN): Hold until recovery to Grade ≤1, then resume at same dose
• Grade 3 ALT or AST (>5 to 20x ULN) OR Grade 3 bilirubin (>3 to 10x ULN): Hold until recovery to Grade ≤1, then resume at next lower dose

• Permanently discontinue

  • Grade 4 ALT/AST (>20x ULN) OR Grade 4 bilirubin (>10x ULN)
  • ALT/AST >3x ULN AND bilirubin >2x ULN

Other adverse reactions

• Grade 3: Hold until recovery to Grade ≤1, then resume at next lower dose level
• Grade 4: Permanently discontinue

Coadministration with strong CYP2C8 inhibitors

• Avoid coadministration; if unavoidable, reduce tucatinib to 100 mg PO BID
• After discontinuing strong CYP2C8 inhibitor for 3 elimination half-lives, resume tucatinib dose taken before initiating inhibitor

Renal impairment

• Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
• Severe (CrCl <30 mL/min): Use in combination with trastuzumab and capecitabine is not recommended; capecitabine is contraindicated in patients with severe renal impairment

Hepatic impairment

• Mild-to-moderate (Child-Pugh A or B): No dosage adjustment necessary
• Severe (Child-Pugh C): Reduce to 200 mg BID

Dosing Considerations

Verify pregnancy status of females of reproductive potential before initiating

Select patients for unresectable or metastatic colorectal cancer

• Based on presence of HER2 overexpression or gene amplification and RAS wild-type