Kadcyla Trastuzumab Emtansine for Injection

1. Indications and Usage
Metastatic Breast Cancer (MBC):
Treatment of patients with HER2-positive MBC who previously received trastuzumab and a taxane chemotherapy regimen. Patients must have had prior treatment in the adjuvant setting or have had disease recurrence within 6 months of completing adjuvant therapy.
Early Breast Cancer (EBC):
Adjuvant treatment for patients with neoadjuvant HER2-positive early breast cancer who have residual invasive disease following neoadjuvant taxane and trastuzumab-based treatment.
2. Dosage and Administration
Route of Administration:
For Intravenous (IV) Infusion ONLY. Rapid IV injection is strictly prohibited.
Recommended Dosage:
Standard Dose: 3.6 mg/kg administered once every 3 weeks (21 days) until disease progression or unacceptable toxicity.
Dose Adjustments: For Grade 3 or 4 liver enzyme elevations, bilirubin elevations, left ventricular dysfunction, thrombocytopenia, pulmonary toxicity, or peripheral neuropathy, temporarily interrupt or permanently discontinue treatment. If resuming after dose reduction, the first reduction is to 3.0 mg/kg, and the second to 2.4 mg/kg.
Critical Administration Instructions:
Preparation: Reconstitute aseptically using Sterile Water for Injection. Gently rotate the vial; do not shake. Dilute immediately into a compatible IV bag (e.g., 0.9% Sodium Chloride).
Infusion Time: The first infusion should be administered over approximately 90 minutes. If the first infusion is tolerated, subsequent infusions can be completed within 30 minutes.
3. Mechanism of Action
Antibody-Drug Conjugate (ADC):
Composed of a humanized anti-HER2 IgG1 monoclonal antibody (trastuzumab) covalently linked to a microtubule inhibitory agent (DM1, a maytansinoid derivative) via a stable thioether linker (MCC).
Targeted Cytotoxicity:
Binds to the HER2 receptor on tumor cells, is internalized, and undergoes lysosomal degradation to release the DM1 payload. DM1 binds to tubulin, disrupting the microtubule network, causing cell cycle arrest at G2/M phase and inducing apoptosis. It also exhibits antibody-dependent cellular cytotoxicity (ADCC).
4. Safety and Warnings
Hepatotoxicity:
Severe hepatic toxicity, including hepatic failure and death, can occur. Liver function tests (LFTs) must be monitored prior to each dose.
Embryo-Fetal Toxicity:
Can cause fetal death. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months after the final dose.
Cardiac Toxicity:
Can cause left ventricular dysfunction. Evaluate left ventricular ejection fraction (LVEF) prior to initiation and periodically during treatment.
Pulmonary Toxicity:
Serious and fatal interstitial lung disease (ILD)/pneumonitis has been reported. Monitor for respiratory symptoms.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions:
Nausea, fatigue, musculoskeletal pain, bleeding, headache, elevated transaminases, thrombocytopenia, and peripheral neuropathy.
Clinical Research Highlights:
In the EMILYA trial, it demonstrated superior progression-free survival and overall response rates compared to trastuzumab plus paclitaxel in the second-line MBC setting. In the ADMIRAL trial, it significantly improved disease-free survival in the EBC adjuvant setting.
6. Drug Interactions
CYP3A4 Inhibitors:
DM1 is a substrate of CYP3A4. Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) may increase DM1 exposure. Avoid concomitant use; if unavoidable, monitor closely for toxicity.
Other Hepatotoxic/Myelosuppressive Drugs:
Caution is required when co-administering with other agents that may cause hepatotoxicity or bone marrow suppression.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Trastuzumab emtansine.
Appearance: White to off-white sterile lyophilized cake or powder.
Packaging: Single-use vial (100 mg or 160 mg).
Storage: Store in the original carton at 2°C to 8°C. Do not freeze.