Perjeta (Pertuzumab)
Monoclonal Antibody for HER2-Positive Breast Cancer
Quick Facts About Perjeta
Key Takeaways About Perjeta
- Dual HER2 blockade: Perjeta is always used together with trastuzumab and chemotherapy, providing a more complete blockade of HER2 signalling than trastuzumab alone
- Proven survival benefit: The CLEOPATRA trial demonstrated a significant improvement in overall survival for patients with metastatic HER2-positive breast cancer treated with the Perjeta combination
- Cardiac monitoring required: Heart function must be assessed before and during treatment, as Perjeta can cause left ventricular dysfunction
- Diarrhoea is the most common side effect: Particularly in the first cycles of treatment; patients over 65 years are at higher risk
- Not safe in pregnancy: Effective contraception is required during treatment and for at least 6 months after the last dose due to potential harm to the foetus
What Is Perjeta and What Is It Used For?
Perjeta (pertuzumab) is a targeted cancer therapy belonging to a group of medicines called monoclonal antibodies. It is specifically designed to treat HER2-positive breast cancer by binding to the HER2 receptor on cancer cells and blocking signals that stimulate tumour growth.
Perjeta contains the active substance pertuzumab, a recombinant humanised monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2). HER2 is a protein found on the surface of some cancer cells. When HER2 is overexpressed – a condition known as HER2-positive cancer – it drives uncontrolled cell division and tumour growth. Approximately 15–20% of all breast cancers are HER2-positive, and these cancers tend to be more aggressive than HER2-negative types.
Perjeta is approved for use in three main clinical settings. First, it is used as first-line treatment for metastatic HER2-positive breast cancer – cancer that has spread to other parts of the body such as the lungs, liver, or bones – in patients who have not previously received anti-HER2 therapy or chemotherapy for metastatic disease. Second, it is used as neoadjuvant treatment (given before surgery) to shrink the tumour and increase the likelihood of achieving a pathological complete response, meaning no invasive cancer is found in the breast or lymph nodes at the time of surgery. Third, it is approved as adjuvant treatment (given after surgery) to reduce the risk of cancer recurrence in patients with early-stage HER2-positive breast cancer at high risk of relapse.
In all approved indications, Perjeta is given in combination with trastuzumab (another anti-HER2 monoclonal antibody) and chemotherapy, typically a taxane such as docetaxel or paclitaxel. This triple combination has demonstrated superior efficacy compared to trastuzumab and chemotherapy alone in multiple landmark clinical trials.
How Does Perjeta Work?
Perjeta works through a distinct mechanism that complements the action of trastuzumab. While both drugs target the HER2 protein, they bind to different parts of the receptor. Trastuzumab binds to subdomain IV of HER2, whereas pertuzumab binds to subdomain II, which is the dimerisation domain. By occupying this critical domain, pertuzumab prevents HER2 from pairing (dimerising) with other members of the HER receptor family, including EGFR (HER1), HER3, and HER4.
This blocking of HER2 dimerisation is clinically important because it shuts down key intracellular signalling pathways – particularly the PI3K/Akt and MAPK pathways – that drive cancer cell survival and proliferation. Additionally, pertuzumab triggers antibody-dependent cell-mediated cytotoxicity (ADCC), a process in which the patient’s own immune cells are recruited to attack and destroy the antibody-coated cancer cells. The combination of pertuzumab and trastuzumab provides a more comprehensive blockade of HER2 signalling than either drug alone, which translates into improved clinical outcomes.
What Should You Know Before Receiving Perjeta?
Before starting Perjeta treatment, your oncologist will evaluate your heart function, pregnancy status, and medical history. Several important precautions and contraindications apply to this medication.
Contraindications
Perjeta must not be used if you have a known hypersensitivity (allergy) to pertuzumab or to any of the excipients in the formulation, including L-histidine, sucrose, polysorbat 20, and glacial acetic acid. If you are unsure whether you may be allergic to any component, discuss this with your doctor or nurse before starting treatment.
Warnings and Precautions
Treatment with Perjeta can affect heart function. Before and during treatment with Perjeta, your doctor will assess your cardiac function using echocardiography or a MUGA (multigated acquisition) scan to measure your left ventricular ejection fraction (LVEF). You should inform your healthcare team about any of the following conditions:
- Heart failure or a history of heart failure, including treatment for serious irregular heartbeat
- Uncontrolled high blood pressure (hypertension)
- Recent heart attack (myocardial infarction)
- Previous cardiac problems related to trastuzumab treatment
- Prior anthracycline chemotherapy (such as doxorubicin or epirubicin) – these drugs can damage the heart muscle and increase the risk of cardiac complications when combined with Perjeta
If significant cardiac decline is detected during treatment, your doctor may temporarily pause or permanently discontinue Perjeta therapy. Cardiac function is typically reassessed every three months during treatment and every six months for at least two years after treatment completion.
Infusion reactions, including allergic and anaphylactic (severe allergic) reactions, can occur during or after Perjeta administration. Your healthcare team will monitor you during the infusion and for 30–60 minutes afterwards. In very rare cases, patients have died due to anaphylactic reactions during Perjeta infusion. If you experience symptoms such as facial swelling, difficulty breathing, chest tightness, or severe dizziness during or after the infusion, inform your nurse or doctor immediately.
When Perjeta is combined with other cancer treatments (trastuzumab and chemotherapy), the number of white blood cells may decrease, and fever may develop. This condition, called febrile neutropenia, increases the risk of serious infections. If you have inflammation of the digestive tract (such as mouth sores or diarrhoea), the risk may be greater. Regular blood tests will be performed to monitor your blood cell counts during treatment.
Diarrhoea
Treatment with Perjeta frequently causes diarrhoea, which can be severe. Patients over 65 years of age have a higher risk of diarrhoea compared to younger patients. Diarrhoea is a condition in which the body produces more watery bowel movements than normal. If you experience severe diarrhoea during your cancer treatment, your doctor may initiate anti-diarrhoeal treatment and may temporarily suspend Perjeta therapy until the diarrhoea is under control. It is important to stay well hydrated and to report persistent diarrhoea to your healthcare team promptly.
Pregnancy and Breastfeeding
Perjeta may cause harm to the developing foetus. Before starting treatment, you must inform your doctor if you are pregnant, think you may be pregnant, or are planning to become pregnant. You should use effective contraception during Perjeta treatment and for at least 6 months after the last dose. If you become pregnant during treatment or within 6 months of your last dose, tell your doctor immediately.
It is not known whether pertuzumab passes into breast milk. You should consult your doctor about whether to breastfeed during or after treatment with Perjeta. Given the potential for serious adverse effects in a nursing infant, a decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of treatment to the mother.
Use in Children and Adolescents
Perjeta should not be used in patients under 18 years of age, as there is insufficient safety and efficacy data for this age group.
Use in Elderly Patients
Patients over 65 years of age who are treated with Perjeta are more likely to experience certain side effects compared to younger patients. These include decreased appetite, decreased red blood cell count (anaemia), weight loss, fatigue, altered or lost sense of taste, weakness, numbness, tingling or prickling sensations (particularly in the feet and legs), and diarrhoea. Dose adjustments are not typically required based on age alone, but closer monitoring may be warranted.
How Does Perjeta Interact with Other Drugs?
Perjeta is always administered in combination with trastuzumab and chemotherapy. Formal drug interaction studies have not been conducted, but several important pharmacological interactions are known, particularly with agents that affect heart function.
Because pertuzumab is a monoclonal antibody that is cleared through catabolism (protein breakdown) rather than by liver enzymes, it is not expected to have the same types of drug interactions as small-molecule drugs. However, certain medications may increase the risk of adverse effects when used alongside Perjeta. Always inform your doctor or nurse about all medications you are taking, including over-the-counter medicines, herbal supplements, and vitamins.
| Drug / Drug Class | Type | Effect | Recommendation |
|---|---|---|---|
| Trastuzumab | Required combination | Complementary HER2 blockade; additive cardiac risk | Always given together; cardiac monitoring required |
| Anthracyclines (doxorubicin, epirubicin) | Major interaction | Increased risk of cardiotoxicity | Avoid concurrent use; if sequential, monitor LVEF closely |
| Docetaxel | Required combination | No significant pharmacokinetic interaction; additive neutropenia | Monitor blood counts regularly |
| Paclitaxel | Alternative combination | No significant pharmacokinetic interaction | Used in neoadjuvant/adjuvant settings |
| Carboplatin | Additional combination | Additive myelosuppression | Monitor blood counts; used in neoadjuvant settings |
Cardiotoxic Agents
The most important drug interaction category for Perjeta involves agents that can damage the heart. Anthracycline chemotherapy agents such as doxorubicin and epirubicin are known to cause cumulative, dose-dependent cardiotoxicity. When these agents are used before or after Perjeta-containing regimens, the risk of cardiac dysfunction may be increased. For this reason, sequential rather than concurrent administration is recommended, and heart function should be monitored frequently during and after treatment transitions.
Other Considerations
Because pertuzumab does not undergo hepatic metabolism, interactions with cytochrome P450 enzyme inhibitors or inducers are not expected. No formal studies have been conducted on the interaction between Perjeta and commonly used medications such as anticoagulants, antihypertensives, or hormonal therapies. Patients receiving Perjeta should discuss all concurrent medications with their oncologist to ensure safe and effective treatment.
What Is the Correct Dosage of Perjeta?
Perjeta is given as an intravenous infusion every 3 weeks. The initial dose is 840 mg administered over 60 minutes, followed by 420 mg over 30–60 minutes for all subsequent infusions. It is always administered in combination with trastuzumab and chemotherapy.
Perjeta is administered by a doctor or nurse in a hospital or clinic setting. The drug is given as an intravenous infusion (drip) directly into a blood vessel. The dosing schedule and treatment duration depend on the clinical indication and how the patient responds to treatment.
| Treatment Setting | Loading Dose | Maintenance Dose | Frequency | Duration |
|---|---|---|---|---|
| Metastatic | 840 mg IV over 60 min | 420 mg IV over 30–60 min | Every 3 weeks | Until disease progression or unacceptable toxicity |
| Neoadjuvant | 840 mg IV over 60 min | 420 mg IV over 30–60 min | Every 3 weeks | 3–6 cycles before surgery |
| Adjuvant | 840 mg IV over 60 min | 420 mg IV over 30–60 min | Every 3 weeks | Up to 1 year (18 cycles total with trastuzumab) |
Adults
The recommended dosing regimen for adult patients is a loading dose of 840 mg administered as an intravenous infusion over 60 minutes for the first cycle, followed by a maintenance dose of 420 mg administered over 30 to 60 minutes every 3 weeks thereafter. Perjeta is given on the same day as trastuzumab and chemotherapy, with Perjeta typically administered first, followed by trastuzumab, and then the chemotherapy agent.
During the first infusion, the patient is closely monitored for 60 minutes after the end of the infusion to watch for any infusion reactions. For subsequent infusions that are well tolerated, the observation period is 30 to 60 minutes. No dose reductions of Perjeta are recommended; if a dose is delayed or missed, it should be administered as soon as possible without waiting for the next planned cycle.
Children
Perjeta is not approved for use in patients under 18 years of age. There are no established dosing recommendations for paediatric patients, and the safety and efficacy of pertuzumab in children and adolescents have not been established.
Elderly
No dose adjustment is required for elderly patients. However, patients over 65 years of age should be monitored more closely for side effects, particularly diarrhoea, fatigue, and decreased blood cell counts. Clinical trial data suggest that elderly patients may experience a higher incidence of certain adverse events, but the overall benefit-risk profile remains favourable.
Missed Dose
If you miss or forget a scheduled Perjeta infusion, contact your healthcare team to reschedule as soon as possible. If more than 6 weeks have elapsed since your last infusion, a re-loading dose of 840 mg will be administered (instead of the standard 420 mg maintenance dose), followed by the usual 420 mg every 3 weeks thereafter.
Overdose
There is limited experience with overdose of pertuzumab in clinical trials. The maximum tolerated dose has not been determined. In the event of an overdose, the patient should be closely monitored for signs and symptoms of adverse reactions, particularly cardiac effects and infusion reactions, and appropriate supportive treatment should be provided. There is no specific antidote for pertuzumab overdose.
What Are the Side Effects of Perjeta?
Like all medicines, Perjeta can cause side effects, although not everyone gets them. The most common side effects include diarrhoea, hair loss, nausea, fatigue, rash, and decreased white blood cell counts. Some side effects, such as cardiac dysfunction and severe infusion reactions, can be serious.
It is important to note that many of the side effects listed below may also be caused by the other medicines given in combination with Perjeta (trastuzumab and chemotherapy). Your healthcare team will help you manage side effects and determine which medication may be responsible. Report any new or worsening symptoms to your doctor or nurse promptly.
- Severe or persistent diarrhoea (7 or more bowel movements per day)
- Febrile neutropenia – decreased white blood cells with fever, increasing infection risk
- Infusion reactions – nausea, fever, chills, fatigue, headache, loss of appetite, joint and muscle pain, flushing
- Anaphylaxis – swelling of face and airways with difficulty breathing (very rare but potentially fatal)
- Heart failure – cough, shortness of breath, swelling in arms or legs
- Tumour lysis syndrome – kidney problems, heart irregularities, seizures (rare)
Very Common
- Diarrhoea
- Hair loss (alopecia)
- Nausea or vomiting
- Fatigue
- Skin rash
- Inflammation of the digestive tract (e.g. mouth sores)
- Decreased red blood cell count (anaemia)
- Joint or muscle pain, muscle weakness
- Constipation
- Decreased appetite
- Altered or lost sense of taste
- Fever
- Swollen ankles or other body parts due to fluid retention
- Insomnia
- Hot flushes
- Numbness, tingling, or prickling sensation, especially in feet and legs (peripheral neuropathy)
- Nosebleeds
- Cough
- Heartburn
- Dry, itchy, or acne-like skin
- Nail disorders
- Sore throat, runny nose, flu-like symptoms
- Increased tear production
- Febrile neutropenia (low white blood cells with fever)
- Body pain, arm and leg pain, abdominal pain
- Shortness of breath
- Dizziness
Common
- Peripheral neuropathy with sharp, shooting, burning, or icy pain; pain from light touch; impaired balance or coordination
- Inflammation of the nail bed (paronychia)
- Ear, nose, or throat infection
- Decreased function of the left ventricle of the heart, with or without symptoms
Uncommon
- Interstitial lung disease – dry cough or shortness of breath due to tissue damage around the air sacs of the lungs
- Pleural effusion – fluid around the lungs causing difficulty breathing
Rare
- Severe anaphylactic reactions during infusion (very rare but potentially life-threatening)
- Tumour lysis syndrome
If you experience any side effects after treatment with Perjeta has ended, contact your doctor immediately and inform them that you have previously been treated with Perjeta. Some side effects may appear or persist after treatment is completed.
How Should Perjeta Be Stored?
Perjeta is stored and handled by healthcare professionals in hospital or clinic settings. Patients do not need to store this medication at home, as it is administered as an intravenous infusion in a healthcare facility.
For healthcare professionals, the following storage conditions apply to Perjeta:
- Store in a refrigerator at 2°C to 8°C (36°F to 46°F)
- Do not freeze – freezing will damage the product
- Keep the vial in the outer carton to protect from light
- Do not use after the expiry date printed on the carton (EXP). The expiry date refers to the last day of the stated month
- Do not use if the solution contains visible particles or has an abnormal colour. The solution should be clear to slightly opalescent, colourless to slightly yellow
- Keep out of sight and reach of children
Once diluted for infusion, the prepared solution should be used immediately. If not used immediately, it may be stored at 2°C to 8°C for up to 24 hours. Any unused portion of the medicinal product or waste material should be disposed of in accordance with local regulations for cytotoxic drugs.
What Does Perjeta Contain?
Each 14 mL vial of Perjeta contains 420 mg of pertuzumab at a concentration of 30 mg/mL, along with inactive excipients that ensure the stability and compatibility of the solution.
The active substance in Perjeta is pertuzumab, a recombinant humanised IgG1 monoclonal antibody produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Each single-use glass vial contains 420 mg of pertuzumab in 14 mL of solution (30 mg/mL).
The excipients (inactive ingredients) are:
- Glacial acetic acid (pH adjustment)
- L-Histidine (buffer)
- Sucrose (stabiliser)
- Polysorbat 20 (surfactant)
- Water for injections
Perjeta contains less than 1 mmol sodium per dose, meaning it is essentially sodium-free. Each 14 mL vial contains 2.8 mg of polysorbat 20, which may cause allergic reactions in some individuals. If you have known allergies to polysorbat, inform your doctor before starting treatment.
Perjeta is supplied as a concentrate for solution for infusion. In its undiluted form, it appears as a clear to slightly opalescent, colourless to slightly yellow liquid. Each pack contains one single-use vial. The marketing authorisation holder is Roche Registration GmbH, Emil-Barell-Strasse 1, D-79639 Grenzach-Wyhlen, Germany.
Frequently Asked Questions About Perjeta
Perjeta (pertuzumab) is a monoclonal antibody used to treat HER2-positive breast cancer. It is approved for three settings: first-line treatment of metastatic HER2-positive breast cancer, neoadjuvant treatment (before surgery) to shrink tumours, and adjuvant treatment (after surgery) to reduce the risk of cancer recurrence. It is always given in combination with trastuzumab and chemotherapy.
Perjeta is given as an intravenous infusion (drip) in a hospital or clinic. The first dose is 840 mg over 60 minutes. All subsequent doses are 420 mg over 30 to 60 minutes, given every 3 weeks. You will be monitored during and after each infusion for potential reactions.
The most common side effects include diarrhoea (which can be severe), hair loss, nausea, fatigue, rash, and decreased white blood cell count. Febrile neutropenia (low white blood cells with fever) can also occur. Most side effects are manageable with appropriate medical support, and your healthcare team will monitor you closely throughout treatment.
Yes, Perjeta can cause left ventricular dysfunction, meaning the heart may not pump as effectively. Your heart function will be assessed before and during treatment using echocardiography or MUGA scans. Patients with pre-existing heart conditions, prior anthracycline use, or uncontrolled hypertension may be at higher risk. If significant cardiac decline is detected, treatment may be temporarily paused or permanently discontinued.
Both Perjeta and trastuzumab target the HER2 receptor, but they bind to different parts of it. Trastuzumab binds to subdomain IV, while Perjeta binds to subdomain II (the dimerisation domain). By using both drugs together, a more complete blockade of HER2 signalling is achieved, which has been shown in clinical trials to improve survival outcomes compared to trastuzumab and chemotherapy alone.
No, Perjeta should not be used during pregnancy. It may cause harm to the developing foetus. Women of childbearing potential must use effective contraception during treatment and for at least 6 months after the last dose. If you become pregnant during treatment, contact your doctor immediately. Your doctor will discuss the potential risks and benefits with you.
References
- Swain SM, Baselga J, Kim SB, et al. Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer (CLEOPATRA study). New England Journal of Medicine. 2015;372(8):724-734. doi:10.1056/NEJMoa1413513
- Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere). Annals of Oncology. 2016;27(6):1064-1072. doi:10.1093/annonc/mdw095
- von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer (APHINITY trial). New England Journal of Medicine. 2017;377(2):122-131. doi:10.1056/NEJMoa1703643
- European Medicines Agency. Perjeta (pertuzumab) – Summary of Product Characteristics. EMA/H/C/002547. Last updated 2025.
- U.S. Food and Drug Administration. PERJETA (pertuzumab) Prescribing Information. Genentech, Inc. Reference ID: 5090825.
- NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 1.2025. National Comprehensive Cancer Network.
- Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO Clinical Practice Guidelines. Annals of Oncology. 2019;30(8):1194-1220. doi:10.1093/annonc/mdz173
- World Health Organization. WHO Model List of Essential Medicines – 23rd List (2023). Geneva: WHO; 2023.
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Medical Review
Content reviewed by the iMedic Medical Review Board – an independent panel of board-certified oncologists and clinical pharmacologists who ensure accuracy according to international guidelines (EMA, FDA, ESMO, NCCN).
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All medical claims are supported by Level 1A evidence from systematic reviews, randomised controlled trials, and international clinical practice guidelines. The GRADE framework is used to assess evidence quality.
Last medical review: | Next scheduled review: June 2026