Trastuzumab — Drug Monograph

Brand names: Herceptin, Ogivri, Herzuma, Ontruzant, Trazimera, Kanjinti

Drug class: Monoclonal Antibody

Mechanism of Action

Humanized anti-HER2 (ErbB2) monoclonal antibody (IgG1κ). Binds to subdomain IV of the extracellular domain of the HER2 receptor. Inhibits downstream PI3K/AKT and MAPK signaling, induces antibody-dependent cellular cytotoxicity (ADCC), and blocks cleavage of the HER2 extracellular domain (preventing formation of constitutively active p95-HER2 fragment).

FDA Indications

• HER2-overexpressing (IHC 3+ or FISH-amplified) breast cancer — adjuvant (node-positive and node-negative with high-risk features); metastatic first- and subsequent-line
• HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma — first-line with cisplatin and fluoropyrimidine

Common Side Effects

• Infusion reactions (first infusion: fever, chills, nausea — usually mild)
• Fatigue
• Headache
• Nausea, diarrhea
• Asymptomatic LVEF decline

Clinical Pearl

Trastuzumab, pertuzumab, and the taxane (THP) is the preferred first-line regimen for HER2-positive metastatic breast cancer. Duration of trastuzumab in early breast cancer is 12 months total (after surgery). For extended adjuvant therapy, neratinib can be added after completing trastuzumab-based therapy in HER2+ breast cancer.

Related Therapies & Mechanisms

• Pertuzumab (Perjeta) — Monoclonal Antibody · Breast
• Margetuximab (Margenza) — Monoclonal Antibody · Breast
• Ramucirumab (Cyramza) — Monoclonal Antibody · Gastric
• Zolbetuximab (Vyloy) — Monoclonal Antibody · Gastric