Instructions for Fam-trastuzumab deruxtecan-nxki

1. Generic name: trastuzumab

Product name: Enhertu/Enhertu

All names: Fam-trastuzumab deruxtecan-nxki, Fam-trastuzumab deruxtecan-nxki, Recombinant trastuzumab lyophilized powder for injection,T-DXd

2. Indications:

1. HER2-positive metastatic breast cancer (MBC): Fam-trastuzumab deruxtecan-nxki is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received an anti-HER2-based regimen, including in the metastatic setting, or in the neoadjuvant or adjuvant setting, and who experience disease recurrence during or within six months of completing treatment.

2. HER2-oligometastatic breast cancer (MBC): Trastuzumab is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 1+ or IHC 2+/ISH-) breast cancer who have previously received chemotherapy in the metastatic setting or who have experienced disease recurrence during or within 6 months of completing adjuvant chemotherapy.

3. Unresectable or metastatic HER2-mutated non-small cell lung cancer (NSCLC): Trastuzumab is indicated for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumors have activating HER2 (ERBB2) mutations and who have received prior systemic therapy.

4. Locally advanced or metastatic gastric cancer (MGC): Trastuzumab is suitable for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have previously received trastuzumab.

3. Usage and dosage:

1. Pre-medication and management: When patients start using trastuzumab, they need to undergo relative gene mutation and tumor sample testing. Do not substitutetrastuzumab or ado-trastuzumab emtansine. Since trastuzumab is an injectable formulation, slow down or interrupt the infusion rate if the patient develops infusion-related symptoms.

2. Recommended dose: Trastuzumab may cause moderate emesis in patients, including delayed nausea and/or vomiting. Take prophylactic antiemetic medications according to local agency guidelines for preventing chemotherapy-induced nausea and vomiting.

(1) Breast cancer (MBC), non-small cell lung cancer (NSCLC): The recommended dose of detrastuzumab is 5.4mg/kg, intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

(2) Gastric cancer (MGC):The recommended dose of trastuzumab is 6.4mg/kg, intravenously infused once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

3. Dose adjustment: If a patient develops adverse reactions after taking trastuzumab, it may be necessary to temporarily interrupt, reduce the dose, or stop treatment with trastuzumab. After reducing the dose, do not increase the dose of trastuzumab. If the scheduled dose is delayed or missed, administer the dose as soon as possible, keeping an interval of 3 weeks between doses If a serious infusion reaction occurs, permanently discontinue trastuzumab.

For patients with breast cancer and non-small cell lung cancer, the first dose of trastuzumab is reduced to 4.4 mg/kg, and the second dose is reduced to 3.2 mg/kg. If further reduction is needed, treatment is stopped. ; For patients with gastric cancer, the first dose of trastuzumab is reduced to 5.4 mg/kg, and the second dose is reduced to 4.4 mg/kg. If further reduction is needed, treatment is stopped.

4. Adverse reactions:

In clinical studies of trastuzumab in the treatment of breast cancer, non-small cell lung cancer, and gastric cancer, the most common (≥20%) adverse reactions (including laboratory abnormalities) were nausea, decreased white blood cell count, decreased hemoglobin, and neutrophils. Decreased cell count, decreased lymphocyte count, fatigue, decreased platelet count, elevated aspartate aminotransferase, vomiting, elevated alanine aminotransferase, alopecia, elevated blood alkaline phosphatase, constipation, musculoskeletal pain, decreased appetite, diarrhea, hypokalemia, elevated blood bilirubin, fever.

5. Storage:

Store vials of trastuzumab in the original carton in a refrigerator at 2°C to 8°C (36°F to 46°F), protected from light, until reconstitution. Do not freeze. Do not shake reconstituted or diluted solutions. If not for immediate use, store reconstituted trastuzumab at room temperature for 4 hours, including preparation and infusion, or in a refrigerator at 2°C to 8°C (36°F to 46°F) protected from light for 24 hours. Do not freeze. Discard any unused portion remaining in the vial. The prepared infusion solution is then stored refrigerated (2°C to 8°C [36°F to 46°F]), allowing the solution to reach room temperature before administration. Cover the infusion bag to protect it from light.

6. Special groups:

1. Women: Pregnant women use trastuzumabCan cause harm to the fetus. It is recommended that females of reproductive potential use effective contraception during drug treatment and for 7 months after the last dose; women are advised not to breastfeed during drug treatment and for 7 months after the last dose.

2. Males: Due to potential genotoxicity, male patients with female partners of reproductive potential are recommended to use effective contraceptive measures during treatment with trastuzumab and within 4 months after the last dose.

7. Mechanism of action:

Trastuzumab is aHER2-directed antibody-drug conjugate which is a humanized antiHER2 IgG1. The small molecule DXd is a topoisomerase I inhibitor linked to an antibody via a cleavable linker. After binding to HER2 on tumor cells, trastuzumab undergoes internalization and intracellular linker cleavage by lysosomal enzymes. After release, membrane-permeable DXd causes DNA damage and apoptotic cell death.