pertuzumab

High Alert

HER2-positive metastatic breast cancer in patients who have not yet been treated with anti-HER2 agents or chemotherapy (in combination with docetaxel and trastuzumab [or trastuzumab hyaluronidase]).
Neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early stage breast cancer (either >2 cm in diameter or node-positive) (in combination with trastuzumab [or trastuzumab hyaluronidase] and chemotherapy).
Adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence (in combination with trastuzumab [or trastuzumab hyaluronidase] and chemotherapy).

Action ⬆ ⬇

A monoclonal antibody that attaches to and blocks the human epidermal growth factor receptor 2 protein (HER2), resulting in cell growth arrest and apoptosis.

Therapeutic effects:

Decreased spread of breast cancer.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 18 days.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	20 mo‡

‡Median duration of response.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy.

Use Cautiously in:

Asian patients (↑ incidence of febrile neutropenia);
Lactation: Safety not established in breastfeeding;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

May reflect combination treatment with docetaxel and trastuzumab.

CV: peripheral edema, HF

Derm: alopecia, rash, dry skin, nail disorder

EENT: ↑lacrimation

GI: ↓appetite, diarrhea, nausea, vomiting

Hemat: anemia, leukopenia, NEUTROPENIA

MS: arthralgia, myalgia

Neuro: dizziness, dysgeusia, fatigue, headache, insomnia, peripheral neuropathy, weakness

Resp: dyspnea

Misc: chills, fever, hypersensitivity reactions (including anaphylaxis and angioedema), infusion reactions

Interactions ⬆ ⬇

Drug-drug:

↑risk of bone marrow depression/immunosuppression with other bone marrow depressants/immunosuppressants or radiation therapy.

Route/Dosage ⬆ ⬇

Metastatic Breast Cancer

IV (Adults ): 840 mg initially, then 420 mg every 3 wk.

Neoadjuvant Treatment of Breast Cancer

IV (Adults ): 840 mg initially, then 420 mg every 3 wk for 3–6 cycles given preoperatively. Following surgery, administer 420 mg every 3 wk to complete 1 yr of treatment (up to 18 cycles).

Adjuvant Treatment of Breast Cancer

IV (Adults ): 840 mg initially, then 420 mg every 3 wk for 1 yr (up to 18 cycles) or until disease recurrence or unacceptable toxicity.

Availability ⬆ ⬇

Solution for injection: 30 mg/mL

Assessment ⬆ ⬇

Assess left ventricular ejection fraction (LVEF) before starting pertuzumab and at regular intervals during therapy. Metastatic Breast Cancer: If pretreatment LVEF ≥50%, monitor prior to and about every 12 wk. If LVEF ↓ to <40% or 40–45% with a fall of ≥10% points below pretreatment value, hold pertuzumab and trastuzumab (or trastuzumab hyaluronidase) for at least 3 wk. If after 3 wk LVEF recovered to >45% or 40–45% with a fall of <10% points below pretreatment value, resume pertuzumab and trastuzumab (or trastuzumab hyaluronidase). Early Breast Cancer: If pretreatment LVEF ≥55%, monitor prior to and about every 12 wk or once neoadjuvant therapy. If LVEF ↓ to <50% with a fall of ≥10% points below pretreatment value, hold pertuzumab and trastuzumab (or trastuzumab hyaluronidase) for at least 3 wk. If after 3 wk LVEF recovered to >50% with a fall of <10% points below pretreatment value, resume pertuzumab and trastuzumab (or trastuzumab hyaluronidase). For patients receiving anthracycline-based chemotherapy, a LVEF of ≥ 50% is required after completion of anthracyclines, before starting pertuzumab and trastuzumab.
- If trastuzumab is withheld or discontinued, withhold or discontinue pertuzumab. If docetaxel is discontinued, pertuzumab and trastuzumab therapy may continue. Dose reductions are not recommended for pertuzumab.
Assess patient closely for 60 min after initial infusion and 30 min after subsequent infusions for signs and symptoms of infusion-associated reactions (pyrexia, chills, fatigue, headache, asthenia, hypersensitivity, vomiting). If a significant infusion-associated reaction occurs, slow or interrupt infusion and administer appropriate medical therapies. Monitor until complete resolution of signs and symptoms. If severe infusion reactions occur, consider discontinuation of pertuzumab.
Monitor patient for signs and symptoms of hypersensitivity reactions (rash, hives, itching, dyspnea, swelling of throat, lips, tongue) occurs.

Lab Test Considerations:

Verify negative pregnancy status before starting therapy.Determine HER protein overexpression prior to therapy.
- Monitor CBC with differential periodically during therapy.

Implementation ⬆ ⬇

IV Administration:

Administer pertuzumab, trastuzumab (or trastuzumab hyaluronidase) and docetaxel sequentially. Administer pertuzumab and trastuzumab or trastuzumab hyaluronidase in any order. Administer docetaxel after pertuzumab and trastuzumab or trastuzumab hyaluronidase. Observe patient for 30 to 60 min after pertuzumab infusion and before any subsequent infusion of trastuzumab or docetaxel.
Intermittent Infusion: Diluent: 0.9% NaCl; do not use D5W. Withdraw appropriate volume of pertuzumab and dilute in 250 mL using a PVC or non-PVC polyolefin infusion bag. Gently invert to mix; do not shake. If not administered immediately, may be refrigerated for 24 hr; do not freeze.
Rate: Infuse initial 840 mg over 60 min, followed every 3 wk by 420 mg over 30–60 min.
For delayed or missed doses, if time between 2 sequential infusions is <6 wk, administer 420 mg dose of pertuzumab; do not wait until next planned dose. If time between 2 sequential infusions ≥6 wk, readminister initial 840 mg dose over 60 min, followed every 3 wk by 420 mg dose over 30–60 min.

Patient/Family Teaching ⬆ ⬇

Explain purpose of medication to patient.
Advise patient to report signs and symptoms of infusion-associated reactions immediately.
Advise patient to notify health care professional immediately if signs and symptoms of left ventricular dysfunction (new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hr, dizziness or loss of consciousness) occur.
Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding. Caution patient to use effective contraception during and for 7 mo following the last dose. Inform patients who become pregnant while receiving pertuzumab of pregnancy pharmacovigilance program to monitor infant outcomes. Encourage pregnant females who may be exposed to pertuzumab during pregnancy to report exposure to the Genentech Adverse Event Line at 1-888-835-2555. Monitor females who become pregnant for oligohydramnios.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇