pertuzumab/trastuzumab/hyaluronidase (Rx)

Brand and Other Names:Phesgo, pertuzumab-trastuzumab-hyaluronidase-zzxf
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

pertuzumab/trastuzumab/hyaluronidase

injectable solution

  • 600mg/600mg/30,000units/10 mL
  • 1,200mg/600mg/30,000units/15 mL

Early Breast Cancer

Neoadjuvant treatment

  • Indicated in combination with chemotherapy for neoadjuvant treatment of adults with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either >2 cm in diameter or node positive as part of a complete treatment regimen for early breast cancer [EBC])
  • Treated with IV pertuzumab and trastuzumab within 6 weeks: 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC initially and then q3Weeks for subsequent administrations
  • Treated with IV pertuzumab and trastuzumab ≥6 weeks: 1,200 mg pertuzumab/600 mg trastuzumab/30,000 units hyaluronidase SC initially followed by 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC q3Weeks for subsequent administrations
  • Administer for 3-6 cycles as part of a treatment regimen for EBC
  • Following surgery
    • Continue to receive pertuzumab/trastuzumab/hyaluronidase to complete 1 year of treatment (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first
    • Refer to the prescribing information for pertuzumab, administered in combination with trastuzumab and chemotherapy, for recommended dose and dosage modifications

Adjuvant treatment

  • Indicated in combination with chemotherapy for adjuvant treatment of adults with HER2-positive EBC at high risk of recurrence
  • Treated with IV pertuzumab and trastuzumab within 6 weeks: 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC initially and then q3Weeks for subsequent administrations
  • Treated with IV pertuzumab and trastuzumab ≥6 weeks: 1,200 mg pertuzumab/600 mg trastuzumab/30,000 units hyaluronidase SC initially followed by 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC q3Weeks for subsequent administrations
  • Administer for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first
  • For taxane-based regimens: Start on Day 1

Metastatic Breast Cancer

Indicated in combination with docetaxel for treatment of adults with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease

Treated with IV pertuzumab and trastuzumab within 6 weeks: 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC initially and then q3Weeks for subsequent administrations

Treated with IV pertuzumab and trastuzumab ≥6 weeks: 1,200 mg pertuzumab/600 mg trastuzumab/30,000 units hyaluronidase SC initially followed by 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC q3Weeks for subsequent administrations

When administered with Phesgo, start with docetaxel is 75 mg/m2 IV initially; may escalate dose to 100 mg/m2 IV q3Weeks if initial dose is well tolerated

Continue until disease progression or unmanageable toxicity, whichever occurs first

Refer to the prescribing information for pertuzumab, administered in combination with trastuzumab and chemotherapy, for recommended dose and dosage modifications

Dosage Modifications

Left ventricular dysfunction (LVEF)

  • If after a repeat assessment within ~3 weeks, the LVEF has not improved, has declined further, and/or the patient is symptomatic, permanently discontinue
  • EBC
    • Pretreatment LVEF: ≥55%
    • Monitor LVEF every ~12 weeks (once during neoadjuvant therapy)
    • Withhold for at least 3 weeks for an LVEF decrease to <50% with a fall of ≥10%-points below pretreatment value
    • Resume after 3 weeks if LVEF has recovered to either LVEF ≥50% OR <10%-points below pretreatment value
    • Before starting Phesgo, patients receiving anthracycline-based chemotherapy require an LVEF ≥50% after completion of anthracyclines
    • If after a repeat assessment within ~3 weeks, LVEF has not improved, has declined further, and/or the patient is symptomatic, permanently discontinue
    • Following completion of Phesgo, continue to monitor for cardiomyopathy and assess LVEF every 6 months for at least 2 years as a component of adjuvant therapy
  • MBC
    • Pretreatment LVEF: ≥50%
    • Monitor LVEF every ~12 weeks
    • Withhold for at least 3 weeks for either an LVEF decrease to <40% OR LVEF decrease to <40-45% with a fall of ≥10%-points below pretreatment value
    • Resume after 3 weeks if LVEF has recovered to either LVEF >40% OR LVEF decrease to <40-45% with a fall of <10%-points below pretreatment value
    • If after a repeat assessment within ~3 weeks, LVEF has not improved, has declined further, and/or the patient is symptomatic, permanently discontinue

Hypersensitivity and administration-related reactions

  • Discontinue immediately if the patient experiences a serious hypersensitivity reaction (eg, anaphylaxis)

Renal impairment

  • All severities: No clinically significant differences in the pharmacokinetics of pertuzumab and trastuzumab were observed

Hepatic impairment

  • Pharmacokinetics of pertuzumab and trastuzumab are unknown

Dosing Considerations

Do not substitute Phesgo for or with pertuzumab, trastuzumab, ado-trastuzumab emtansine, or fam-trastuzumab deruxtecan

No dose adjustments are required for patient body weight or for concomitant chemotherapy regimen

Patient selection

  • Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens by an FDA-approved companion diagnostic test
  • Information on the FDA-approved tests are available at: http://www.fda.gov/CompanionDiagnostics

Safety and efficacy not established

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Interactions

Interaction Checker

and pertuzumab/trastuzumab/hyaluronidase

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    Contraindicated

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          Minor

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            Adverse Effects

            >10%

            All grades

            • Low hemoglobin (90%)
            • Low absolute lymphocytes (89%)
            • High creatinine (84%)
            • Low total leukocytes (82%)
            • Alopecia (77%)
            • Low total absolute neutrophils (68%)
            • Nausea (60%)
            • Diarrhea (60%)
            • High ALT (58%)
            • High AST (50%)
            • Anemia (36%)
            • Asthenia (31%)
            • Fatigue (29%)
            • Low platelets (27%)
            • Stomatitis (25%)
            • Myalgia (25%)
            • Arthralgia (24%)
            • Constipation (22%)
            • Neutropenia (22%)
            • Vomiting (20%)
            • Radiation skin injury (19%)
            • Decreased appetite (17%)
            • Dysgeusia (17%)
            • Headache (17%)
            • Insomnia (17%)
            • Low potassium (17%)
            • Low albumin (16%)
            • Peripheral sensory neuropathy (16%)
            • Rash (16%)
            • Mucosal inflammation (15%)
            • Injection site reaction (15%)
            • Dry skin (15%)
            • Cough (15%)
            • Dyspepsia (14%)
            • Pyrexia (13%)
            • Dizziness (13%)
            • Procedural pain (13%)
            • High potassium (13%)
            • Low sodium (13%)
            • Epistaxis (12%)
            • Peripheral neuropathy (12%)
            • Hot flush (12%)
            • Decreased weight (11%)
            • Upper respiratory tract infection (11%)

            Grade 3-4

            • Low absolute lymphocytes (37%)
            • Low total absolute neutrophils (30%)
            • Low total leukocytes (25%)
            • Neutropenia (14%)

            1-10%

            All grades

            • Paresthesia (10%)
            • Back pain (10%)
            • High bilirubin (9%)
            • Low glucose (9%)
            • Nail discoloration (9%)
            • Erythema (9%)
            • Hemorrhoids (9%)
            • Abdominal pain (9%)
            • Leukopenia (9%)
            • Upper abdominal pain (8%)
            • Peripheral edema (8%)
            • High sodium (7%)
            • Malaise (7%)
            • Febrile neutropenia (7%)
            • Dermatitis (7%)
            • Nail disorder (7%)
            • Bone pain (7%)
            • Pain in extremity (6%)
            • Muscle spasms (6%)
            • Musculoskeletal pain (6%)
            • Palmoplantar erythrodysesthesia syndrome (6%)
            • Influenza-like illness (5%)

            Grade 3-4

            • Febrile neutropenia (7%)
            • Diarrhea (7%)
            • Low potassium (5.2%)
            • Low hemoglobin (2.8%)
            • Leukopenia (2.4%)
            • Fatigue (2%)
            • Nausea (2%)
            • Anemia (1.6%)
            • High ALT (1.6%)
            • Hypokalemia (1.6%)
            • High potassium (1.2%)
            • Dyspnea (1.2%)

            <1%

            Grade 3-4

            • High sodium (0.8%)
            • Mucosal inflammation (0.8%)
            • High AST (0.8%)
            • Decreased appetite (0.8%)
            • Decreased weight (0.8%)
            • Paresthesia (0.8%)
            • Peripheral sensory neuropathy (0.8%)
            • Vomiting (0.8%)
            • Stomatitis (0.8%)
            • Palmoplantar erythrodysesthesia syndrome (0.8%)
            • Asthenia (0.4%)
            • Abdominal pain (0.4%)
            • Peripheral neuropathy (0.4%)
            • Low sodium (0.4%)
            • Lacrimation increased (0.4%)
            • Dry eye (0.4%)
            • Radiation skin injury (0.4%)
            • Paronychia (0.4%)
            • Urinary tract infection (0.4%)
            • Cough (0.4%)
            • Musculoskeletal pain (0.4%)
            • Myalgia (0.4%)
            • Dry skin (0.4%)
            • Rash (0.4%)

            Postmarketing Reports

            Glomerulopathy

            Immune thrombocytopenia

            Tumor lysis syndrome

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            Warnings

            Black Box Warnings

            Cardiomyopathy

            • Administration can result in subclinical and clinical cardiac failure
            • Incidence and severity was highest in patients receiving Phesgo with anthracycline-containing chemotherapy regimens
            • Evaluate cardiac function before and during treatment
            • Discontinue Phesgo in patients receiving adjuvant therapy and withhold in patients with metastatic disease for clinically significant decrease in LVEF

            Embryofetal toxicity

            • Exposure to Phesgo can result in embryofetal death and birth defects, including oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death
            • Advise patients of these risks and the need for effective contraception

            Pulmonary toxicity

            • Administration can result in serious and fatal pulmonary toxicity
            • Discontinue for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome; monitor until symptoms completely resolve

            Contraindications

            Hypersensitivity to pertuzumab, trastuzumab, hyaluronidase, or any of its excipients

            Cautions

            Hypertension, arrhythmias, left ventricular cardiac dysfunction, disabling cardiac failure, cardiomyopathy, and cardiac death may occur

            May cause fetal harm when administered to a pregnant female

            Serious and fatal pulmonary toxicity reported

            May cause exacerbation of chemotherapy-induced neutropenia

            Severe administration-related reactions, including hypersensitivity, anaphylaxis, and events with fatal outcomes, have been associated with IV pertuzumab and trastuzumab

            Drug interaction overview

            • Patients who receive anthracycline after stopping Phesgo may be at increased risk of cardiac dysfunction because of the long washout period of Phesgo
            • If possible, avoid anthracycline-based therapy for up to 7 months after stopping Phesgo
            • If anthracyclines are used, carefully monitor cardiac function
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            Pregnancy & Lactation

            Pregnancy

            May cause fetal harm when administered to a pregnant female

            In postmarketing reports, use of IV trastuzumab during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death

            Verify pregnancy status of females of reproductive potential before initiation

            Animal data

            • Pertuzumab
              • In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryofetal deaths at clinically relevant exposures that were 2.5- to 20-fold greater than exposures in humans receiving the recommended dose, based on peak plasma concentration
            • Trastuzumab
              • In studies in which IV trastuzumab was administered to pregnant cynomolgus monkeys during organogenesis at doses up to 25 mg/kg given twice weekly (up to 25x the recommended weekly human dose of 2 mg/kg), trastuzumab crossed the placental barrier during the early (gestation days 20 to 50) and late (gestation days 120 to 150) phases of gestation

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for 7 months after the last dose

            Clinical considerations

            • Monitor females who received treatment during pregnancy or within 7 months prior to conception for oligohydramnios
            • If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care

            Pregnancy pharmacovigilance program

            • If administered during pregnancy, or if a patient becomes pregnant during treatment or within 7 months following the last dose, healthcare providers and patients should immediately report exposure to Genentech at 1-888-835-2555

            Lactation

            No information available on the presence of pertuzumab, trastuzumab, or hyaluronidase in human milk, the effects on the breastfed infant, or the effects on milk production

            Published data suggest that human IgG is present in human milk but does not enter the neonatal and infant circulation in substantial amounts

            Trastuzumab was present in the milk of lactating cynomolgus monkeys but was not associated with neonatal toxicity

            Take into account that the elimination half-life of pertuzumab and trastuzumab washout period is 7 months when considering the mother’s clinical need for treatment

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Pertuzumab

            • Monoclonal antibody that binds to the extracellular dimerization domain of the human epidermal growth factor receptor 2 protein (HER2); mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells that overexpress HER2

            Trastuzumab

            • Monoclonal antibody; inhibits growth of tumor cells that overexpress HER2

            Hyaluronidase

            • Human hyaluronidase increases permeability of SC tissue by temporarily depolymerizing hyaluronan
            • Effects are reversible and permeability of SC tissue is restored within 24-48 hr

            Absorption

            Plasma trough concentration

            • Pertuzumab (Cycle 7): 88.7 mcg/mL (SC); 72.4 mcg/mL (IV)
            • Trastuzumab (Cycle 7): 58.7 mcg/mL (SC); 44.1 mcg/mL (IV)

            Absolute bioavailability

            • Pertuzumab: 0.7
            • Trastuzumab: 0.8

            Peak plasma time

            • Pertuzumab: 4 days
            • Trastuzumab: 4 days

            Distribution

            Vd

            • Pertuzumab: 2.8 L
            • Trastuzumab: 2.9L

            Elimination

            Clearance

            • Pertuzumab: 0.2 L/day
            • Trastuzumab: 0.1 L/day
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            Administration

            SC Compatibility

            Compatible with stainless steel, polypropylene, polycarbonate, polyethylene, polyurethane, polyvinyl chlorid and fluorinated ethylene polypropylene

            SC Preparation

            Check vial labels to ensure the drug being prepared and administered is Phesgo and not IV pertuzumab, IV trastuzumab, or SC trastuzumab

            Visually inspect vials for particulate matter and discoloration before administration, whenever solution and container permit; do not use if particulates or discoloration is present

            Do not shake

            Discard any unused portion remaining in the vial

            Each vial is ready-to-use for one SC injection and should not be diluted

            Withdraw dose from the vial

            Use 25- to 27-gauge (3/8-5/8 inch) hypodermic injection needles to inject dose

            To avoid needle clogging, attach needle to the syringe immediately before administration, followed by volume adjustment to 15 mL (initial dose) and 10 mL (maintenance dose)

            Replace the transfer needle with a syring-closing cap if the dose is not administered immediately and the drug has been withdrawn into the syringe; label syringe

            Label the syringe with the peel-off sticker

            SC Administration

            SC use only; do not administer IV

            Phesgo has different dosage and administration instructions than IV pertuzumab, IV trastuzumab, and SC trastuzumab when administered alone

            Do not substitute Phesgo for or with pertuzumab, trastuzumab, ado-trastuzumab emtansine, or fam-trastuzumab deruxtecan

            Observe for a minimum of 30 min after initial dose and 15 min after each maintenance dose for signs or hypersensitivity symptoms or administration-related reactions

            Medications to treat such reactions, as well as emergency equipment, should be available for immediate use

            During the treatment course, other SC medications should be injected at different sites

            Administration site

            • Alternate between the left and right thigh only
            • Administer new injections at least 1 inch (2.5 cm) from the previous site on healthy skin and never into areas where the skin is red, bruised, tender, or hard
            • Do not split the dose between 2 syringes or between 2 sites of administration

            Administration time

            • 1,200 mg pertuzumab/600 mg trastuzumab/30,000 units /15 mL: Administer SC over ~8 min
            • 600 mg pertuzumab/600 mg trastuzumab/30,000 units/10 mL: Administer SC over ~5 min

            Sequence of administration

            • Anthracycline-based regimen (EBC): Administer Phesgo following completion of the anthracycline
            • Docetaxel- or paclitaxel- based regimen (EBC): Administer docetaxel or paclitaxel after Phesgo
            • Docetaxel-based regimen (MBC): Administer docetaxel after Phesgo

            Missed or delayed dose

            • Time between 2 sequential injections is <6 weeks: Administer 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC; do not wait until the next planned dose
            • Time between 2 sequential injections is ≥6 weeks: Re-administer 1,200 mg pertuzumab/600 mg trastuzumab/30,000 units hyaluronidase SC, followed by 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC q3Weeks
            • For chemotherapy dose modifications, see relevant prescribing information

            Storage

            Unopened vial

            • Refrigerate at 2-8ºC (36-46ºF)
            • Protect from light
            • Do not freeze; do not shake

            Drug withdrawn from vial into syringe

            • Refrigerate at 2-8ºC (36-46ºF) for up to 24 hr and store at room temperature (20-25ºC [68-77ºF]) for up to 4 hr
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            Images

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            Formulary

            FormularyPatient Discounts

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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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