pertuzumab and trastuzumab

L01FY01

Forms & Strengths

Fixed-dose combination injection: 600 mg pertuzumab / 600 mg trastuzumab per 10 mL (60 mg/mL of each) in a single-dose vial
Fixed-dose combination injection: 1200 mg pertuzumab / 600 mg trastuzumab per 15 mL (80 mg/mL pertuzumab and 40 mg/mL trastuzumab) in a single-dose vial (subcutaneous)

Adult Dosing

Initial loading dose: 1200 mg pertuzumab / 600 mg trastuzumab subcutaneous injection administered over approximately 8 minutes
Maintenance dose: 600 mg pertuzumab / 600 mg trastuzumab subcutaneous injection every 3 weeks administered over approximately 5 minutes
Administer in combination with intravenous chemotherapy (e.g., docetaxel) for metastatic breast cancer or as part of a neoadjuvant/adjuvant regimen

Pediatric Dosing

Indications

Adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence, in combination with chemotherapy
Neoadjuvant treatment of HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (tumor > 2 cm or node-positive) as part of a regimen containing chemotherapy
Treatment of HER2-positive metastatic breast cancer in combination with docetaxel for patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease

Mechanism of Action

Pertuzumab is a monoclonal antibody that targets the extracellular dimerization domain (Subdomain II) of the HER2 receptor, blocking ligand-dependent heterodimerization with other HER family receptors (EGFR, HER3, HER4)
Trastuzumab is a monoclonal antibody that binds to subdomain IV of the extracellular domain of the HER2 receptor, inhibiting ligand-independent signaling and mediating antibody-dependent cellular cytotoxicity (ADCC)
Combination of pertuzumab and trastuzumab provides dual HER2 receptor blockade, resulting in synergistic inhibition of tumor cell growth and enhanced apoptosis in HER2-overexpressing tumors

Contraindications

Known hypersensitivity to pertuzumab, trastuzumab, murine proteins, or any component of the product formulation
Severe left ventricular cardiac dysfunction (pre-treatment LVEF below institutional limits of normal or baseline LVEF < 50%)

Adverse Reactions

Cardiotoxicity, including left ventricular dysfunction and congestive heart failure
Infusion-related and injection site reactions (e.g., chills, fever, rash, pain)
Myelosuppression leading to neutropenia, leukopenia, and anemia
Gastrointestinal disturbances including diarrhea, nausea, vomiting, and stomatitis
Alopecia, fatigue, peripheral neuropathy, and arthralgia

Drug Interactions

Anthracyclines: Increased risk of cardiac toxicity and left ventricular dysfunction when administered sequentially or concurrently
Cardiotoxic drugs: Increased risk of additive cardiac depression
No formal pharmacokinetic drug-drug interactions have been observed between pertuzumab and trastuzumab when administered as a fixed-dose combination

Curated Content: Needs Vetting Before Put to Clinical Use