Pertuzumab

Mechanism of action

◎HER2 (ErbB2) receptor tyrosine kinase, extracellular dimerisation domain IIPertuzumab

ⓘ The crystal shows the extracellular region of human HER2 with the pertuzumab Fab bound to domain II, the arm HER2 uses to pair with other HER receptors.

Pertuzumab is a humanised IgG1 antibody that binds domain II of HER2, a different site from trastuzumab, which binds domain IV. Domain II is where HER2 pairs with HER3 and other HER receptors, so pertuzumab stops ligand-driven heterodimers from forming and from sending growth and survival signals. Bound to the tumour cell, it can also trigger antibody-dependent cellular cytotoxicity. Using both antibodies blocks HER2 more completely than either alone.

1. Pertuzumab binds HER2 domain II (trastuzumab binds domain IV)
2. HER2 can no longer pair with HER3 and other HER receptors
3. Growth and survival signalling stops; immune cells attack

Indications

• HER2-positive breast cancer (early, locally advanced, inflammatory or metastatic), with trastuzumab and chemotherapy such as docetaxel. Breast cancer →

Adverse effects

Common

• Diarrhoea, nausea, mouth sores
• Hair loss, dry skin, nail changes
• Numbness or tingling in the hands and feet
• Watery eyes, loss of appetite, trouble sleeping

Contraindications

• Use at the same time as cardiotoxic anthracyclines

Key interactions

Anthracyclines (e.g., doxorubicin)

Add cardiotoxicity to the HER2 blockade; pertuzumab is not combined with cardiotoxic anthracyclines at the same time.

Trastuzumab

Intended combination: the two antibodies bind different HER2 domains and their effects add up, as do the heart risks.

What is monitored

• Heart function (ejection fraction) before and during treatment
• HER2 test on the tumour before starting
• Pregnancy test before starting in women who could be pregnant
• Vital signs during and after each infusion

Administration and safety

• Intravenous infusion by a doctor or nurse; the patient is observed during and after each infusion.
• The subcutaneous pertuzumab-trastuzumab-hyaluronidase product is a different preparation and is not swapped for the intravenous ones.

Pregnancy and breastfeeding

Avoid in pregnancy. Can cause fetal harm; a pregnancy test is done before starting, and effective contraception is used during treatment and for several months after.

Nursing care

• Confirm a recent heart function test before each phase of treatment.
• Teach the patient to report breathlessness, cough, swollen ankles, rapid heartbeat or sudden weight gain.
• Watch for swelling of the face, wheeze, fever or chills during the infusion.
• Teach effective contraception during treatment and for months after the last dose.

Pharmacokinetics

Absorption

Intravenous infusion; a combined product with trastuzumab and hyaluronidase is injected under the skin.

Half-life

Long, about 18 days (median), which allows dosing every three weeks.

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Connections

← Back to the class: Antineoplastic monoclonal antibodies

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Pertuzumab Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex (RCSB Protein Data Bank, 2004).

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Representative model, for educational purposes only.