LuciTuca（Tucatinib Tablets） TUKYSA 150mg

English Name: Tucatinib

[Specification] 150 mg/tablet; 60 tablets/bottle.

[Summary]

Tucatinib is a tyrosine kinase inhibitor of HER2. *In vitro*, tucatinib inhibits the phosphorylation of HER2 and HER3, thereby inhibiting downstream MAPK and AKT signaling as well as cell proliferation, and demonstrates anti-tumor activity in HER2-expressing tumor cells. *In vivo*, tucatinib inhibits the growth of HER2-expressing tumors. The combination of tucatinib and trastuzumab demonstrates increased anti-tumor activity—both *in vitro* and *in vivo*—compared to either drug used alone.

[Indications]

1. Metastatic Breast Cancer:

In combination with trastuzumab and capecitabine, for the treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer—including those with brain metastases—who have previously received one or more anti-HER2-based regimens in the metastatic setting.

2. Unresectable or Metastatic Colorectal Cancer:

In combination with trastuzumab, for the treatment of adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer who have progressed following chemotherapy based on a fluoropyrimidine, oxaliplatin, and irinotecan.

[Dosage and Administration]

1. Metastatic Breast Cancer:

The recommended dosage is 300 mg orally twice daily, in combination with trastuzumab and capecitabine, until disease progression or unacceptable toxicity.

2. Unresectable or Metastatic Colorectal Cancer:

The recommended dosage is 300 mg orally twice daily, in combination with trastuzumab, until disease progression or unacceptable toxicity.

3. For patients with severe hepatic impairment, the recommended dosage is 200 mg orally twice daily. 【Adverse Reactions】

1. Serious Side Effects: Diarrhea, liver disease, pruritus (itching), yellowing of the skin or eyes, dark brown urine, pain in the upper right abdomen, severe fatigue, decreased appetite, easy bleeding or bruising.

2. Common Side Effects: Diarrhea, redness and swelling of the palms or soles, pain, swelling or appearance of rashes/blisters, oral ulcers, decreased appetite, abdominal pain, nausea, fatigue, elevated liver function test levels, vomiting, headache, anemia, skin rash, impairment of male and female fertility.

【Precautions】

1. Diarrhea: Tucatinib can cause severe diarrhea, including dehydration, hypotension, acute kidney injury, and death. Diarrhea occurred in 81% of patients treated with tucatinib; of these, 12% experienced Grade 3 diarrhea and 0.5% experienced Grade 4 diarrhea. If diarrhea occurs, administer anti-diarrheal treatment as clinically indicated. Depending on the severity of the diarrhea, interrupt the dosage, then reduce the dosage or permanently discontinue tucatinib.

2. Hepatotoxicity: Monitor ALT (alanine aminotransferase), AST (aspartate aminotransferase), and bilirubin levels every 3 weeks prior to initiating tucatinib treatment. Depending on the severity of the hepatotoxicity, reduce the dosage or permanently discontinue tucatinib.

3. Embryo-fetal Toxicity: Women of reproductive potential are advised to use effective contraception during treatment; male patients of reproductive potential are advised to use effective contraception during treatment with tucatinib and for at least 1 week after the last dose.

【Efficacy and Safety】

The median overall survival (OS) for the tucatinib triplet regimen was 21.9 months (95% CI, 18.3–31.0), whereas the median overall survival (OS) for treatment with trastuzumab and capecitabine alone was 17.4 months (95% CI, 13.6–19.9) (HR, 0.66; 95% CI, 0.50–0.88; P = 0.0048). The 1-year and 2-year overall survival (OS) rates for the tucatinib group and the control group were 76% and 62%, and 45% and 27%, respectively. The OS benefit was maintained across all prespecified subgroups.

Compared with trastuzumab and capecitabine alone, the addition of the small-molecule TKI tucatinib also resulted in a 46% reduction in the risk of disease progression or death, with a median progression-free survival (PFS) of 7.8 months (95% CI, 7.5–9.6) versus 5.6 months (95% CI, 4.2–7.1) (HR, 0.54; 95% CI, 0.42–0.71; P < 0.00001). The 6-month and 1-year PFS rates were 63% and 46%, and 33% and 12%, respectively. The PFS benefit was consistent across all clinically relevant prespecified subgroups.

[Storage]

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).