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);
Rep: Women of reproductive potential;
Lactation: Safety not established in breastfeeding;
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 ↓ of ≥10% points below pretreatment value, hold pertuzumab and trastuzumab (or trastuzumab hyaluronidase) for ≥3 wk. If after 3 wk, LVEF recovered to >45% or 40–45% with a ↓ 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 during neoadjuvant therapy. If LVEF ↓ to <50% with a ↓ of ≥10% points below pretreatment value, hold pertuzumab and trastuzumab (or trastuzumab hyaluronidase) for ≥3 wk. If after 3 wk, LVEF recovered to >50% with a ↓ of <10% points below pretreatment value, resume pertuzumab and trastuzumab (or trastuzumab hyaluronidase). For patients receiving anthracycline-based chemotherapy, a LVEF ≥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 ↓ are not recommended for pertuzumab.
Assess patient closely for 60 min after initial infusion and 30 min after subsequent infusions for signs/symptoms of infusion-associated reaction (fever, chills, fatigue, headache, asthenia, hypersensitivity, vomiting). If a significant infusion-associated reaction occurs, slow or interrupt infusion and treat as indicated. Monitor until complete resolution of reaction. If severe infusion reactions occur, consider discontinuation of pertuzumab.
Monitor patient for signs and symptoms of hypersensitivity reactions (rash, hives, itching, dyspnea, angioedema) occurs. If hypersensitivity reaction occurs, immediately discontinue pertuzumab. Keep medications and emergency equipment available for immediate use.

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 taxane sequentially. Administer pertuzumab and trastuzumab (or trastuzumab hyaluronidase) in any order. Administer taxane after pertuzumab and trastuzumab (or trastuzumab hyaluronidase).
- Observe patient for 30–60 min after pertuzumab infusion and before any subsequent infusion of trastuzumab or taxane.
Intermittent Infusion: Diluent: Withdraw appropriate volume of pertuzumab and dilute in 250 mL of 0.9% NaCl using a PVC or non-PVC polyolefin infusion bag. Gently invert to mix; do not shake. Administer immediately, or refrigerate for 24 hr; do not freeze.
Rate: Infuse initial dose over 60 min and following doses 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, followed every 3 wk by 420 mg dose.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to report signs/symptoms of infusion-associated and hypersensitivity reactions immediately.
Advise patient to notify health care provider immediately if signs/symptoms of left ventricular dysfunction (new onset or worsening shortness of breath, cough, swelling of ankles/legs, swelling of face, palpitations, weight gain of >5 pounds in 24 hr, dizziness or loss of consciousness) occur.
Instruct patient to notify health care provider 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; or dyspnea occur. 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 provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider immediately if pregnancy is planned or suspected or if breastfeeding. Caution patient to use effective contraception during therapy and for 7 mo following last dose. Inform patients who become pregnant while receiving pertuzumab of pregnancy pharmacovigilance program to monitor infant outcomes. Encourage patient to report exposure to Genentech Adverse Event Line: 1-888-835-2555. Monitor exposed pregnant patients for oligohydramnios.

Evaluation/Desired Outcomes ⬆ ⬇

Decreased spread of breast cancer.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

50242- Genentech, Inc.
- 50242-144-
  - 50242-144-02- 300 L in 1 TANK (50242-144-02)

50242- Genentech, Inc.
- 50242-145- PERJETA
  - 50242-145-01- 1 VIAL, SINGLE-USE in 1 CARTON (50242-145-01) / 14 mL in 1 VIAL, SINGLE-USE

67643- Lonza Biologics, Inc.
- 67643-7002-
  - 67643-7002-1- 120000 mL in 1 TANK (67643-7002-1)

67643- Lonza Biologics, Inc.
- 67643-7002-
  - 67643-7002-2- 300000 mL in 1 TANK (67643-7002-2)

67643- Lonza Biologics, Inc.
- 67643-7003-
  67643-7003-1- 300000 mL in 1 TANK (67643-7003-1)

67643- Lonza Biologics, Inc.
- 67643-7003-
  67643-7003-2- 120000 mL in 1 TANK (67643-7003-2)

67643- Lonza Biologics, Inc.
- 67643-7004-
  67643-7004-1- 120000 mL in 1 TANK (67643-7004-1)

67643- Lonza Biologics, Inc.
- 67643-7004-
  67643-7004-2- 300000 mL in 1 TANK (67643-7004-2)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇