🧬 Introduction & Generic Name

Tukysa (tucatinib) is a kinase inhibitor used in combination with trastuzumab and capecitabine to treat adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

• Generic Name: Tucatinib

• Brand Name: Tukysa

• Manufacturer: Seagen Inc. & licensed by Pfizer

• Drug Class: HER2-selective tyrosine kinase inhibitor

• Indications:

  1. HER2‑positive metastatic breast cancer — in combination with trastuzumab and capecitabine, including those with brain metastases, after prior anti-HER2 therapy .

  2. RAS wild-type, HER2-positive metastatic colorectal cancer — combined with trastuzumab after progression on fluoropyrimidine, oxaliplatin, and irinotecan .

💊 Dosage

• Standard adult dose: 300 mg orally twice daily, ~12 hours apart, with or without food .

• With capecitabine/trastuzumab (breast cancer): Capecitabine is dosed at 1,000 mg/m² twice daily with meals .

• Dose adjustments:

  • 1st reduction: 250 mg twice daily

  • 2nd: 200 mg twice daily

  • 3rd: 150 mg twice daily; discontinue if still not tolerated .

⚠️ Side Effects

        Very Common:

• Diarrhea (up to 81%; ~12% grade 3–4)

• Nausea, vomiting

• Palmar‑plantar erythrodysesthesia (hand‑foot rash)

• Rash

• Stomatitis (mouth sores)

• Fatigue

• Elevated liver enzymes (AST/ALT)

• Anemia, decreased appetite

       Other Possible Effects:

• Fever, infusion reactions (colorectal cancer regimen)

🔍 Warnings & Precautions

1. Diarrhea: Severe diarrhea may cause dehydration, hypotension, kidney injury, or death. Monitor closely and manage promptly with anti-diarrheals. Interrupt or reduce dose if grade ≥3.

2. Hepatotoxicity: Monitor liver enzymes before treatment and every 3 weeks; dose reductions or discontinuation may be needed

3. Fertility: May impair fertility—both males and females should use contraception during treatment and for 1 week afterward

4. Contraindications/cautions:

   • Severe hepatic impairment: dose adjustment recommended.

   • Severe renal impairment in capecitabine regimen not recommended .

   • Breastfeeding: avoid during and 1 week after last dose .

✅ Conclusion

Tukysa is a potent, targeted oral therapy for advanced HER2-positive cancers, either breast or colorectal, offering benefits even in patients with brain metastases. However, vigilant monitoring for severe diarrhea and liver toxicity, as well as dose adjustments, are essential. Discuss potential benefits and risks with your oncologist to ensure safe and optimal use.