Kadcyla Trastuzumab Emtansine for Injection

1. Indications and Usage
Early Breast Cancer (EBC):
Indicated as a single agent for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based therapy.
Metastatic Breast Cancer (MBC):
Indicated as a single agent for the treatment of patients with HER2-positive metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either received prior treatment for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy.
2. Dosage and Administration
Route of Administration:
For Intravenous (IV) Infusion ONLY. Do not administer as an IV push or bolus.
Recommended Dosage:
Dose: 3.6 mg/kg body weight.
Schedule: Administered once every 3 weeks (21-day cycle).
Administration Instructions:
First Infusion: Administer over 90 minutes. Observe the patient for at least 90 minutes post-infusion.
Subsequent Infusions: If well tolerated, administer over 30 minutes. Observe the patient for at least 30 minutes post-infusion.
Treatment Duration:
Early Breast Cancer: A total of 14 cycles unless disease recurrence or unacceptable toxicity occurs.
Metastatic Breast Cancer: Until disease progression or unacceptable toxicity.
Missed Dose:
If a dose is delayed or missed, administer it as soon as possible; do not wait until the next planned cycle. Adjust the schedule to maintain a 3-week interval.
3. Mechanism of Action
Antibody-Drug Conjugate (ADC):
Trastuzumab emtansine combines a humanized anti-HER2 IgG1 monoclonal antibody (trastuzumab) covalently linked to a microtubule inhibitor (DM1, a maytansine derivative) via a stable thioether linker (MCC).
Targeted Cytotoxicity:
Upon binding to the HER2 receptor subdomain IV, the conjugate undergoes receptor-mediated internalization and lysosomal degradation, releasing DM1 intracellularly. DM1 binds to tubulin, disrupting the microtubule network, leading to cell cycle arrest and apoptotic cell death. It also retains the ADCC and HER2 signaling inhibition properties of trastuzumab.
4. Safety and Warnings
Hepatotoxicity:
Can cause severe liver injury, including nodular regenerative hyperplasia, portal hypertension, and hepatic failure. Monitor liver function tests (AST/ALT and bilirubin) prior to each dose. Dose reduction or permanent discontinuation is required for severe elevations.
Cardiac Toxicity:
Can cause left ventricular dysfunction. Assess LVEF prior to initiation and periodically during treatment. Discontinue if symptomatic heart failure or significant LVEF decline occurs.
Embryo-Fetal Toxicity:
Can cause fetal harm. Females of reproductive potential must use effective contraception during treatment and for at least 7 months after the final dose.
Pulmonary Toxicity:
Interstitial lung disease (ILD) and pneumonitis can occur. Permanently discontinue Kadcyla in patients diagnosed with ILD or pneumonitis.
Bleeding & Thrombocytopenia:
Severe and fatal bleeding events have occurred. Monitor platelet counts before each dose. Interrupt or reduce the dose for severe thrombocytopenia.
5. Adverse Reactions
Most Common (Incidence ≥25%):
Fatigue, nausea, musculoskeletal pain, hemorrhage, headache, elevated transaminases, thrombocytopenia, and peripheral neuropathy.
Serious Adverse Reactions (>0.5%):
Hemorrhage, pyrexia, thrombocytopenia, dyspnea, abdominal pain, musculoskeletal pain, and vomiting.
6. Drug Interactions
No formal drug-drug interaction studies have been conducted. Because DM1 is metabolized by CYP3A4/5 and is a P-gp substrate, caution is advised when co-administering with strong CYP3A4 inhibitors or inducers, though clinical significance is currently unknown.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Trastuzumab emtansine.
Excipients: Succinic acid, sodium hydroxide, polysorbate 20, sucrose.
Appearance: White to off-white sterile lyophilized powder cake for IV infusion.
Storage:
Store vials refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Reconstituted solutions must be stored at 2°C–8°C and used within 24 hours.