Pertuzumab (Perjeta)

How Pertuzumab Works

HER2 is a receptor on the surface of cells that sends “grow” signals. In about 15 to 20 percent of breast cancers the cells carry far too much HER2, which drives fast growth. These cancers are called HER2-positive.

HER2 sends its strongest signals when it pairs up (dimerizes) with a partner receptor, especially HER3. Pertuzumab attaches to the part of HER2 used for this pairing (the dimerization domain, subdomain II) and stops the pair from forming. Trastuzumab binds a different part of HER2 (subdomain IV). Because they block HER2 in complementary ways, giving both together suppresses the cancer's growth signals more completely. Both antibodies also flag the cancer cells for attack by the immune system.

What Pertuzumab Is Used For

Pertuzumab is FDA-approved only for HER2-positive breast cancer, in three settings:

Metastatic breast cancer (first-line)

• With trastuzumab and docetaxel for HER2-positive metastatic breast cancer not previously treated with HER2-targeted therapy or chemotherapy for metastatic disease (FDA approval 2012)
• In the CLEOPATRA trial, adding pertuzumab improved median overall survival from about 41 months to about 57 months at the final analysis
• After chemotherapy stops, pertuzumab and trastuzumab are often continued as maintenance, sometimes with hormone therapy if the cancer is also hormone receptor-positive

Before surgery (neoadjuvant)

• With trastuzumab and chemotherapy for locally advanced, inflammatory or early-stage HER2-positive breast cancer larger than 2 cm or node-positive
• Increases the chance that no invasive cancer is found at surgery (pathological complete response), which can make surgery easier and helps guide treatment afterwards

After surgery (adjuvant)

• With trastuzumab and chemotherapy for early HER2-positive breast cancer at high risk of coming back, for example when lymph nodes are involved (FDA approval 2017)
• In the APHINITY trial the overall benefit was modest and was concentrated in people with node-positive disease, which is why it is generally reserved for higher-risk cancers

Common Regimens Containing Pertuzumab

Pertuzumab and trastuzumab are not given at the same time as anthracyclines such as doxorubicin because of the combined heart risk; they start after the anthracycline part is finished.

Dosing and Administration

Intravenous pertuzumab (Perjeta)

• Loading dose: 840 mg infused over about 60 minutes
• Then: 420 mg every 3 weeks, infused over 30 to 60 minutes
• The dose is fixed and does not depend on body weight
• You are observed for a short time after each infusion for reactions
• If a dose is delayed by 6 weeks or more, the loading dose is usually repeated

Phesgo (injection under the skin)

• Contains pertuzumab, trastuzumab and hyaluronidase in one vial (FDA approval 2020)
• Injected into the thigh by a healthcare professional: about 8 minutes for the first dose and about 5 minutes for later doses, every 3 weeks
• Avoids the need for a drip for the antibodies; chemotherapy, if given, is still intravenous
• Injection-site redness or pain is common; effectiveness is similar to the intravenous drugs

How long treatment lasts

• Early breast cancer: a total of one year of HER2-targeted treatment (up to 18 doses), including doses given before surgery
• Metastatic breast cancer: until the cancer grows or side effects become unacceptable

Side Effects

Pertuzumab is almost always given with trastuzumab and chemotherapy, so it can be hard to tell which drug causes which effect. The list below highlights what is most linked to pertuzumab.

Most linked to pertuzumab

• Diarrhoea: the most common; usually mild to moderate and most frequent during the chemotherapy part. Start loperamide as advised, drink plenty, and call your team for 4 or more extra stools a day, diarrhoea at night, or diarrhoea with fever or dizziness. See managing diarrhoea.
• Rash and dry skin, nail changes
• Infusion or injection reactions: chills, fever, tiredness or headache during or soon after a dose; occasionally more serious allergic reactions
• Fatigue and nausea

Mostly from the chemotherapy given with it

• Hair loss, which usually recovers after chemotherapy ends
• Low white blood cell counts and infection risk (neutropenia); adding pertuzumab can make low counts with fever slightly more common
• Peripheral neuropathy (numbness or tingling) from taxanes
• Mouth sores

Serious but less common

• Reduced heart pumping function or heart failure (see below)
• Severe allergic reactions
• Harm to an unborn baby

Heart Monitoring

Like trastuzumab, pertuzumab can lower the left ventricular ejection fraction (LVEF), a measure of how strongly the heart pumps. In trials, adding pertuzumab to trastuzumab did not substantially increase heart problems compared with trastuzumab alone, but monitoring is still required.

• An echocardiogram or MUGA scan before starting and about every 3 months during treatment
• If LVEF falls significantly, treatment is paused and the scan repeated; most people recover and many can restart
• Extra care if you have had anthracyclines, chest radiotherapy, high blood pressure or existing heart disease
• Report breathlessness, swollen ankles, a racing heartbeat or sudden weight gain

Precautions

• Pregnancy: must be avoided; use effective contraception during treatment and for 7 months after the last dose. Do not breastfeed during treatment; ask your team how long to wait afterwards.
• Vaccines: inactivated vaccines such as flu and COVID vaccines are generally fine; ask about timing during chemotherapy and avoid live vaccines while chemotherapy is ongoing.
• Other medicines: pertuzumab has no important known drug-drug interactions, but tell your team about all medicines and supplements.
• Hormone therapy: if the cancer is also hormone receptor-positive, hormone therapy is often given alongside or after HER2-targeted treatment.

Frequently Asked Questions