Active Ingredient: Tucatinib
Tucatinib is indicated in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least 2 prior anti-HER2 treatment regimens.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 300 milligrams tucatinib, 2 times daily.
The recommended dose is 300 mg tucatinib (two 150 mg tablets) taken twice daily continuously in combination with trastuzumab and capecitabine, at doses described in table 1. Refer to the summary of product characteristics (SmPC) for co-administered trastuzumab and capecitabine for additional information. The treatment components can be administered in any order.
Table 1. Recommended dosing:
| Treatment | Dose | Treatment days | Timing relative to food intake |
|---|---|---|---|
| Tucatinib | 300 mg orally twice daily | Continuously | With or without a meal |
| Capecitabine | 1.000 mg/m² orally twice daily | Days 1 to 14 every 21 days | Within 30 minutes after a meal |
| Trastuzumab Intravenous dosing Initial dose Subsequent doses OR Subcutaneous dosing | 8 mg/kg intravenously 6 mg/kg intravenously 600 mg subcutaneously | Day 1 Every 21 days Every 21 days | Not applicable |
Treatment with tucatinib should be continued until disease progression or unacceptable toxicity.
In the case of a missed dose, the patient should take their next dose at the regularly scheduled time.
The recommended tucatinib dose modifications for patients with adverse reactions are provided in Tables 2 and 3. Refer to the SmPC for co-administered trastuzumab and capecitabine for dose modifications for toxicities suspected to be caused by those therapies.
Table 2. Recommended tucatinib dose reductions for adverse reactions:
| Dose level | Tucatinib dose |
|---|---|
| Recommended starting dose | 300 mg twice daily |
| First dose reduction | 250 mg twice daily |
| Second dose reduction | 200 mg twice daily |
| Third dose reduction | 150 mg twice daily1 |
1 TUKYSA should be permanently discontinued in patients unable to tolerate 150 mg orally twice daily.
Table 3. Recommended tucatinib dose modifications for adverse reactions:
| Adverse Reaction | Severity1 | Tucatinib dosage modification |
|---|---|---|
| Diarrhoea | Grade 1 and 2 | No dose modification is required. |
| Grade 3 without anti-diarrheal treatment | Initiate or intensify appropriate medical therapy. Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the same dose level. | |
| Grade 3 with anti-diarrheal treatment | Initiate or intensify appropriate medical therapy. Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the next lower dose level. | |
| Grade 4 | Permanently discontinue tucatinib. | |
| Increased ALT, AST or bilirubin2 | Grade 1 bilirubin (> ULN to 1.5 x ULN) | No dose modification is required. |
| Grade 2 bilirubin (>1.5 to 3 × ULN) | Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the same dose level. | |
| Grade 3 ALT or AST (>5 to 20 × ULN) OR Grade 3 bilirubin (>3 to 10 × ULN) | Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the next lower dose level. | |
| Grade 4 ALT or AST (>20 × ULN) OR Grade 4 bilirubin (>10 × ULN) | Permanently discontinue tucatinib. | |
| ALT or AST >3 × ULN AND Bilirubin >2 × ULN | Permanently discontinue tucatinib. | |
| Other adverse reactions | Grade 1 and 2 | No dose modification is required. |
| Grade 3 | Hold tucatinib until recovery to ≤ Grade 1, then resume tucatinib at the next lower dose level. | |
| Grade 4 | Permanently discontinue tucatinib. |
1 Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03
2 Abbreviations: ULN = upper limit of normal; ALT = alanine aminotransferase; AST = aspartate aminotransferase
Tucatinib should be taken approximately 12 hours apart, at the same time every day, with or without a meal. Tucatinib may be taken at the same time with capecitabine.
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