Pertuzumab + Trastuzumab

• HER2-Positive Breast Cancer:
• In combination with chemotherapy for neoadjuvant treatment of early-stage HER2-positive breast cancer.
• In combination with chemotherapy for metastatic or locally advanced HER2-positive breast cancer.
• HER2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma:
• In combination with chemotherapy for advanced or metastatic disease (trastuzumab component approved; pertuzumab use in this setting may be off-label or investigational).

• Route: Intravenous infusion.
• Pertuzumab Dosage:
• Loading dose: 840 mg IV over 60 minutes on Day 1.
• Maintenance dose: 420 mg IV over 30–60 minutes every 3 weeks.
• Trastuzumab Dosage:
• Loading dose: 8 mg/kg IV over 90 minutes on Day 1 (first dose).
• Maintenance dose: 6 mg/kg IV over 30–90 minutes every 3 weeks.
• Duration: Continue combination therapy until disease progression or unacceptable toxicity.
• Dose Adjustments:
• No specific adjustments for renal impairment.
• Use with caution in severe hepatic impairment.
• Infusion reactions may require slowing or interrupting the infusion.
• Pediatric Use: Safety and efficacy not established.

Pertuzumab and trastuzumab are recombinant humanized monoclonal antibodies targeting distinct epitopes on the extracellular domain of the human epidermal growth factor receptor 2 (HER2). Pertuzumab binds to subdomain II, blocking receptor dimerization, especially heterodimerization with HER3, thereby inhibiting ligand-activated signaling pathways critical for tumor cell proliferation and survival. Trastuzumab binds to subdomain IV, inhibiting HER2 receptor shedding, promoting receptor internalization and degradation, and mediating antibody-dependent cellular cytotoxicity (ADCC). The combination produces a complementary and more comprehensive blockade of HER2 signaling, leading to enhanced inhibition of tumor growth and improved clinical outcomes.

• Absorption: Both drugs administered intravenously with 100% bioavailability.
• Distribution: Volume of distribution approximately 3–4 L for pertuzumab and 2.5–3 L for trastuzumab, mainly in plasma and extracellular fluid.
• Metabolism: Catabolized by proteolytic enzymes into peptides and amino acids; not metabolized by cytochrome P450 enzymes.
• Half-life:
• Pertuzumab: ~18 days.
• Trastuzumab: ~28.5 days.
• Elimination: Cleared via reticuloendothelial system; not excreted unchanged in urine or feces.

• Pregnancy: Both drugs are FDA Category D. Animal studies demonstrate fetal harm; use only if benefits outweigh risks.
• Lactation: Unknown if excreted in human milk. Breastfeeding is not recommended during treatment and for at least 6 months after last dose due to potential serious adverse reactions in infants.

• Class: Antineoplastic agents
• Subclass: Monoclonal antibodies targeting HER2 receptor

• Known hypersensitivity to pertuzumab, trastuzumab, or any excipients.
• Severe cardiac dysfunction or recent myocardial infarction.

• Cardiotoxicity: Both agents carry risk of decreased left ventricular ejection fraction (LVEF) and congestive heart failure; monitor cardiac function before and during therapy. Avoid use if baseline LVEF <50%.
• Infusion-Related Reactions: Monitor during and after infusion; symptoms may include fever, chills, rash, hypotension.
• Pregnancy Risk: Effective contraception required during and after treatment.
• Diarrhea and Neutropenia: Common with pertuzumab; monitor and manage accordingly.
• Hypersensitivity: Severe anaphylactic reactions may occur; be prepared to manage.

• Common: Diarrhea, alopecia, nausea, fatigue, rash, neutropenia, peripheral neuropathy, infusion-related reactions.
• Serious: Cardiac dysfunction (heart failure, reduced LVEF), severe infusion reactions, infections secondary to neutropenia.

• No significant CYP450-mediated interactions due to monoclonal antibody metabolism.
• Caution when combined with other cardiotoxic agents (e.g., anthracyclines).
• No known drug-food or drug-alcohol interactions.

• Current clinical guidelines (NCCN, ESMO) recommend pertuzumab plus trastuzumab with chemotherapy as first-line treatment for HER2-positive metastatic breast cancer.
• Expanded indications include neoadjuvant therapy for early HER2-positive breast cancer.
• No new major safety warnings; cardiac monitoring remains essential.

• Store both drugs refrigerated at 2°C to 8°C (36°F to 46°F).
• Do not freeze or shake.
• Protect from light; keep in original carton until use.
• Use immediately after dilution; do not store diluted solutions for prolonged periods.