Tucatinib, when used in combination with other drugs such as trastuzumab, significantly enhances anti-tumor efficacy and provides a new treatment option for HER2 positive cancer patients.

1、 Indications

Tucatinib is a kinase inhibitor, which is used in combination with trastuzumab and capecitabine to treat adult HER2 positive breast cancer patients:

Advanced unresectable or metastatic breast cancer (including patients with brain metastasis)

Patients with metastatic diseases who have received at least one anti-HER2 regimen in the past

2、 Mechanism of action

Tukatinib is a HER2 tyrosine kinase inhibitor that works by:

Inhibition of HER2 and HER3 phosphorylation

Blocking downstream MAPK and AKT signaling pathways

Inhibit tumor cell proliferation

Combination therapy with trastuzumab monotherapy can enhance anti-tumor activity

3、 Usage and dosage

Standard dosing regimen

Recommended dose: 300mg orally, twice daily (with an interval of about 12 hours), in combination with trastuzumab and capecitabine

Can be taken with food or on an empty stomach

Swallow the whole piece, do not chew, crush, or pry open

If the missed dose is ≤ 12 hours, it can be supplemented, and if it is>12 hours, the current dose will be skipped

After vomiting, there is no need to take additional medication. Follow the original plan to take the next dose

Dose adjustment

Liver dysfunction:

Child Pugh Grade C: Reduce to 200mg twice a day

Adverse reaction management:

First reduction: 250mg twice a day

Secondary reduction: 200mg twice a day

Three dose reduction: 150mg twice a day

When unable to tolerate 150mg, the medication should be permanently discontinued

4、 Common side effects

≥ 20% incidence rate:

Diarrhea (81%, grade 3 12%)、Hand foot syndrome (63%)、Disgusting (58%)、tired、Hepatotoxicity (42%)、vomiting、stomatitis、Loss of appetite、abdominal pain、headache、anaemia、rash

Important Note

Severe diarrhea: incidence rate of 25%, may lead to dehydration, acute kidney injury, and even death

Hepatotoxicity: 8% of patients have ALT>5 × ULN, and 6% have AST>5 × ULN

5、 Medication precautions

Important monitoring

Before treatment and every 3 weeks: liver function (ALT/AST/bilirubin), complete blood cell count

Regular monitoring: electrocardiogram (QT interval), electrolytes, renal function

Drug interactions

Avoid combination use: Strong CYP3A inducer/Medium acting CYP2C8 inducer

Caution: CYP3A/P-gp substrate drugs (may need to be reduced)

Strong CYP2C8 inhibitor: Reduce to 100mg twice daily

patient education

Avoid grapefruit, starfruit, and pomegranate

Diarrhea ≥ 4 times/day, seek medical attention immediately

Pay attention to liver toxicity symptoms (jaundice, darkened urine color, etc.)

Wash the capsule powder immediately after contact with the skin

6、 Medication for special populations

Pregnancy/lactation

Pregnancy: There is a risk of teratogenicity, and effective contraception is required during treatment and one week after discontinuation of medication

Breastfeeding: Breastfeeding is prohibited during treatment and for one week after discontinuation of medication

Liver and kidney dysfunction

Child Pugh C: Reduce to 200mg twice a day

Severe kidney damage: Not recommended for use (due to contraindications of capecitabine)

Elderly patients

Patients aged 65 and above have a higher incidence of serious adverse reactions (34% vs 24%)

Pediatric drugs

The safety and effectiveness have not yet been established.

Tucatinibinformation