pertuzumab


pertuzumab

Perjeta

Pharmacologic class: Recombinant humanized monoclonal antibody

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Exposure to pertuzumab can result in embryo-fetal death and birth defects. Studies in animals have resulted in oligohydramnios, delayed renal development, and death. Advise patients of these risks and the need for effective contraception.

Action

Targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor (EGRF) 2 protein (HER2) and thereby blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGRF, HER3, and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein kinase and phosphoinositide 3-kinase. Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity.

Availability

Solution for injection: 420 mg/14-ml single-use vial

Indications and dosages

➣ HER2-positive metastatic breast cancer in patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease

Adults: Initially, 840 mg by 60-minute I.V. infusion, followed by 420 mg over 30 to 60 minutes by I.V. infusion q 3 weeks thereafter. When administered with trastuzumab, recommended initial dose of trastuzumab is 8 mg/kg by 90-minute I.V. infusion, followed by 6 mg/kg over 30 to 90 minutes by I.V. infusion q 3 weeks thereafter. When administered with docetaxel, recommended initial dose of docetaxel is 75 mg/m2 by I.V. infusion; may escalate to 100 mg/m2 q 3 weeks if initial dose is well tolerated.

Dosage adjustment

• Left ventricular ejection fraction (LVEF) less than 40% or LVEF of 40% to 45% with a 10% or greater absolute decrease below pretreatment values

Contraindications

None

Precautions

Use cautiously in:

• pregnant and breastfeeding patients

• children (safety and efficacy not established).

Administration

• Be aware that HER2 testing should be performed for selection of patients appropriate for treatment with this drug.

• Assess LVEF before starting drug.

• Verify pregnancy status before starting drug.

See Administer as an I.V. infusion only. Don't give as an I.V. push or bolus.

• Withdraw appropriate volume of drug solution from vial(s). Dilute in a 250-ml normal saline solution-in only PVC or non-PVC polyolefin infusion bag. Mix diluted solution by gentle inversion. Don't shake and don't mix with other drugs. Don't use dextrose (5%) solution.

• Administer immediately once prepared. If diluted infusion solution isn't used immediately, it can be stored at 2° C to 8° C (36° F to 46° F) for up to 24 hours.

See Observe patient closely for 60 minutes after first infusion. If significant infusion-associated reaction occurs, slow or interrupt infusion and administer appropriate medical therapies. Discontinue drug immediately if patient develops a serous hypersensitivity reaction.

• Be aware that drug should be withheld or discontinued if trastuzumab treatment is withheld or discontinued. If docetaxel is discontinued, treatment with pertuzumab and trastuzumab may continue.

• Be aware that pertuzumab dosage reductions aren't recommended.

Adverse reactions

CNS: headache, dizziness, fatigue, peripheral neuropathy, asthenia, insomnia

CV: left ventricular dysfunction

EENT: increased lacrimation, nasopharyngitis

GI: nausea, vomiting, diarrhea, constipation, stomatitis

Hematologic: anemia, leukopenia, neutropenia, febrile neutropenia

Musculoskeletal: myalgia, arthralgia

Respiratory: upper respiratory tract infection, dyspnea, pleural effusion

Skin: alopecia, rash, nail disorder, pruritus, dry skin, paronychia

Other: mucosal inflammation, pyrexia, dysgeusia, decreased appetite, peripheral edema, infusion and hypersensitivity reactions including anaphylaxis

Interactions

None

Patient monitoring

See Closely monitor patient for 30 minutes after each subsequent infusion for infusion and hypersensitivity reactions. If a significant infusion-associated reaction occurs, slow or interrupt infusion and administer appropriate medical therapies. Monitor patients carefully until complete resolution of signs and symptoms. Consider permanent discontinuation in patients with severe infusion reactions.

See Continue to assess LVEF at regular intervals (every 3 months) during treatment to ensure LVEF is within institution's normal limits. If LVEF is less than 40%, or is 40% to 45% with a 10% or greater absolute decrease below pretreatment value, withhold pertuzumab and trastuzumab and repeat LVEF assessment within approximately 3 weeks. Discontinue pertuzumab and trastuzumab if LVEF hasn't improved or has declined further, unless benefits to patient outweigh risks.

• Monitor women who become pregnant during pertuzumab therapy for oligohydramnios. If oligohydramnios occurs, perform fetal testing appropriate for gestational age and consistent with community standards of care.

Patient teaching

See Tell patient to immediately report fever, chills, fatigue, headache, vomiting, weakness, rash, muscle pain, leg swelling, or shortness of breath.

• Advise female patient of childbearing potential to use effective contraception while receiving this drug and for 6 months after last dose.

• Advise breastfeeding patient that she should decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of drug for her treatment.

• As appropriate, review all other significant and life-threatening adverse reactions mentioned above.

pertuzumab

(per-tue-zue-mab) pertuzumab,

Perjeta

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: her2 neu receptor antagonists
Pregnancy Category: D

Indications

Treatment of HER2-positive metastatic breast cancer in patients who have not yet been treated with anti-HER2 agents or chemotherapy; used in combination with docetaxel and trastuzumab.Neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early stage breast cancer (either >2 cm in diameter or node-positive); used in combination with docetaxel and trastuzumab

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 metastatic breast cancer.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.Distribution: Unknown.Metabolism and Excretion: Unknown.Half-life: 18 days.

Time/action profile

ROUTEONSETPEAKDURATION
IVunknownunknown20 mo†
† Median duration of response.

Contraindications/Precautions

Contraindicated in: Hypersensitivity Obstetric: Avoid use during pregnancy; Lactation: Discontinue drug or discontinue breast feeding.Use Cautiously in: HER2 testing is required prior to treatment;genetic implication Asian patients (↑ incidence of febrile neutropenia); Obstetric: Women with reproductive potential; Pediatric: Safe and effective use in pediatric patients has not been established.

Adverse Reactions/Side Effects

May reflect combination treatment with docetaxel and trastuzumab.

Central nervous system

  • dizziness (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)
  • insomnia (most frequent)
  • weakness (most frequent)

Ear, Eye, Nose, Throat

  • ↑ lacrimation (most frequent)

Respiratory

  • dyspnea (most frequent)

Cardiovascular

  • ↓ left ventricular ejection fraction (LVEF)
  • peripheral edema (most frequent)

Gastrointestinal

  • ↓ appetite (most frequent)
  • diarrhea (most frequent)
  • dysgeusia (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Dermatologic

  • alopecia (most frequent)
  • rash (most frequent)
  • dry skin
  • itching
  • nail disorder

Hematologic

  • anemia
  • leukopenia
  • neutropenia (life-threatening)

Musculoskeletal

  • athralgia (most frequent)
  • myalgia (most frequent)

Neurologic

  • peripheral neuropathy (most frequent)

Miscellaneous

  • allergic reactions including anaphylaxis
  • chills (most frequent)
  • infusion reactions (most frequent)
  • fever (most frequent)
  • hypersensitivity reactions (most frequent)

Interactions

Drug-Drug interaction

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

Route/Dosage

Metastatic Breast Cancer

Intravenous (Adults) 840 mg initially, then 420 mg every 3 wk. If less than 6 wk passes between infusions, continue with 420 mg dosing, if 6 wk or more passes between infusions, restart with initial 840 mg dose followed by 420 mg every 3 wk.

Neoadjuvant Treatment of Breast Cancer

Intravenous (Adults) 840 mg initially, then 420 mg every 3 wk for 3–6 cycles given preoperatively. If less than 6 wk passes between infusions, continue with 420 mg dosing, if 6 wk or more passes between infusions, restart with initial 840 mg dose followed by 420 mg every 3 wk.

Availability

Solution for intravenous injection requires dilution: 420 mg/14 mL vial

Nursing implications

Nursing assessment

  • Monitor left ventricular ejection fraction (LVEF) prior to and every 3 mo with metastatic disease and every 6 wk in neoadjuvant setting during therapy. If LVEF drops to <40% or LVEF of 45–49% with a ≥10% absolute decrease below pretreatment values withhold pertuzumab and trastuzumab and repeat LVEF within 3 wks. Pertuzumab may be resumed if LVEF >45% or to 40–45% associated with a <10% absolute decrease below pretreatment values. If after a repeat assessment LVEF has not improved or further declined, discontinue pertuzumab and trastuzumab, unless benefits outweigh risks. Patients who received anthracyclines are at increased risk for ↓ LVEF.
    • 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.
  • Lab Test Considerations: genetic implication Determine HER protein overexpression prior to therapy.
    • Verify pregnancy status prior to initiation of pertuzumab.
    • Monitor CBC with differential periodically during therapy.

Potential Nursing Diagnoses

Decreased cardiac output (Adverse Reactions)

Implementation

  • Intravenous Administration
  • When administered with pertuzumab, initial dose of trastuzumab is 8 mg/kg infused over 90 min, followed every 3 wks by 6 mg/kg infused over 30–90 min.
  • When administered with pertuzumab, initial dose of docetaxel is 75 mg/m2 as an IV infusion. Dose of docetaxel may be ↑ to 100 mg/m2every 3 wks if initial dose is tolerated.
  • Administer pertuzumab, trastuzumab, and docetaxel. Administer pertuzumab and trastuzumab in any order. Administer docetaxel after pertuzumab and trastuzumab. 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 hrs.
  • Rate: Infuse initial 840 mg over 60 min, followed every 3 wks 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, re-administer 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.
  • 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.
  • Advise female patient that pertuzumab is teratogenic and to notify health care professional immediately if pregnancy is planned or suspected or if breast feeding. Caution patient to use effective contraception during and for 6 mo following the last dose. Women who are breast feeding should be advised to discontinue nursing or discontinue pertuzumab. Encourage women who may be exposed during pregnancy to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 and report exposure to the Genentech Adverse Event Line at 1-888-835-2555. Monitor patients who become pregnant for oligohydramnios.

Evaluation/Desired Outcomes

  • Decreased spread of metastatic breast cancer.