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Pertuzumab, Trastuzumab, And Hyaluronidase-Zzxf

FDA Drug Information • Also known as: Phesgo

Brand Names
Phesgo
Drug Class
HER2/neu Receptor Antagonist [EPC], Endoglycosidase [EPC]
Route
SUBCUTANEOUS
Dosage Form
INJECTION, SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: CARDIOMYOPATHY, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY WARNING: CARDIOMYOPATHY, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY See full prescribing information for complete boxed warning. Cardiomyopathy: PHESGO administration can result in subclinical and clinical cardiac failure manifesting as CHF, and decreased LVEF, with greatest risk when administered concurrently with anthracyclines. Evaluate cardiac function prior to and during treatment. Discontinue PHESGO for cardiomyopathy. ( 2.3 , 5.1 ) Embryo-fetal Toxicity: Exposure to PHESGO can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception. ( 5.2 , 8.1 , 8.3 ) Pulmonary Toxicity: Discontinue PHESGO for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. ( 5.3 ) Cardiomyopathy PHESGO administration can result in subclinical and clinical cardiac failure. The incidence and severity were highest in patients receiving PHESGO with anthracycline-containing chemotherapy regimens. Evaluate cardiac function prior to and during treatment with PHESGO. Discontinue PHESGO treatment in patients receiving adjuvant therapy and withhold PHESGO in patients with metastatic disease for clinically significant decrease in left ventricular function [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ] . Embryo-fetal Toxicity Exposure to PHESGO can result in embryo-fetal 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 [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1) , (8.3) ]. Pulmonary Toxicity PHESGO administration can result in serious and fatal pulmonary toxicity. Discontinue PHESGO for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Monitor patients until symptoms completely resolve [see Warnings and Precautions (5.3) ].

Description

11 DESCRIPTION PHESGO is a combination of pertuzumab, trastuzumab, and hyaluronidase. Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). Pertuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture. Pertuzumab has an approximate molecular weight of 148 kDa. Trastuzumab is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2. Trastuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture. Trastuzumab has a molecular weight of approximately 148 kDa. Hyaluronidase (recombinant human) is an endoglycosidase used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously. It is a glycosylated single-chain protein produced by mammalian (Chinese Hamster Ovary) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). Hyaluronidase (recombinant human) has a molecular weight of approximately 61 kDa. PHESGO (pertuzumab, trastuzumab, and hyaluronidase-zzxf) injection is a sterile, preservative-free, clear to opalescent, and colorless to slightly brownish solution supplied in single-dose vials for subcutaneous administration. PHESGO injection is supplied as two different configurations: PHESGO is supplied in a 15 mL single-dose vial containing 1,200 mg of pertuzumab, 600 mg of trastuzumab, and 30,000 units of hyaluronidase, and α,α-trehalose (397 mg), L-histidine (6.75 mg), L-histidine hydrochloric monohydrate (53.7 mg), L-methionine (22.4 mg), polysorbate 20 (6 mg), and sucrose (685 mg) with a pH of 5.5. PHESGO is supplied in a 10 mL single-dose vial containing 600 mg of pertuzumab, 600 mg of trastuzumab, and 20,000 units of hyaluronidase, and α,α-trehalose (397...

What Is Pertuzumab, Trastuzumab, And Hyaluronidase-Zzxf Used For?

1 INDICATIONS AND USAGE PHESGO is a combination of pertuzumab and trastuzumab, HER2/neu receptor antagonists, and hyaluronidase, an endoglycosidase, indicated for: Use in combination with chemotherapy as: neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. ( 1.1 ) adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence ( 1.1 ) Use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. ( 1.2 ) 1.1 Early Breast Cancer (EBC) PHESGO is indicated for use in combination with chemotherapy for the neoadjuvant treatment of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer [see Dosage and Administration (2.2) and Clinical Studies (14.2) ] . the adjuvant treatment of adult patients with HER2-positive early breast cancer at high risk of recurrence [see Dosage and Administration (2.2) and Clinical Studies (14.2) ] . Select patients for therapy based on an FDA-approved companion diagnostic test [see Dosage and Administration (2.1) ]. 1.2 Metastatic Breast Cancer (MBC) PHESGO is indicated for use in combination with docetaxel for the treatment of adult patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease [see Dosage and Administration (2.2) and Clinical Studies (14.1) ] . Select patients for therapy based on an FDA-approved companion diagnostic test [see Dosage and Administration (2.1) ].

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For subcutaneous use in the thigh only. ( 2.2 ) PHESGO has different dosage and administration instructions than intravenous pertuzumab and trastuzumab products. ( 2.2 ) Do not administer intravenously. ( 2.2 ) Perform HER2 testing using FDA-approved tests by laboratories with demonstrated proficiency. ( 1 , 2.1 ) The initial dose of PHESGO is 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase administered subcutaneously over approximately 8 minutes, followed every 3 weeks by a dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase administered subcutaneously over approximately 5 minutes. ( 2.2 ) Neoadjuvant: administer PHESGO by subcutaneous injection every 3 weeks and chemotherapy by intravenous infusion preoperatively for 3 to 6 cycles. ( 2.2 ) Adjuvant: administer PHESGO by subcutaneous injection every 3 weeks and chemotherapy by intravenous infusion postoperatively for a total of 1 year (up to 18 cycles). ( 2.2 ) MBC: administer PHESGO by subcutaneous injection and docetaxel by intravenous infusion every 3 weeks. ( 2.2 ) 2.1 Patient Selection Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage (1) and Clinical Studies (14) ] . Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency. Information on the FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results. 2.2 Important Dosage and Administration Information PHESGO is for subcutaneous use only in the thigh. Do not administer intravenously. PHESGO has different dosage and administration instructions than intravenous pertuzumab, intravenous trastuzumab, and subcutaneous trastuzumab when administered alone. Do not substitute PHESGO for or with pertuzumab, trastuzumab, ado-trastuzumab emtansine, or fam-trastuzumab deruxtecan. PHESGO must always be administered by a healthcare professional. In patients receiving an anthracycline-based regimen for early breast cancer, administer PHESGO following completion of the anthracycline. In patients receiving PHESGO for early breast cancer with docetaxel or paclitaxel, administer docetaxel or paclitaxel after PHESGO. In patients receiving PHESGO for metastatic breast cancer with docetaxel, administer docetaxel after PHESGO. Observe patients for a minimum of 30 minutes after initial dose of PHESGO and 15 minutes after each maintenance dose of PHESGO for signs or hypersensitivity symptoms or administration-related reactions. Medications to...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Cardiomyopathy [see Warnings and Precautions (5.1) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.2) ] Pulmonary Toxicity [see Warnings and Precautions (5.3) ] Exacerbation of Chemotherapy-Induced Neutropenia [see Warnings and Precautions (5.4) ] Hypersensitivity and Administration-Related Reactions [see Warnings and Precautions (5.5) ] Neoadjuvant and Adjuvant Treatment of Breast Cancer The most common adverse reactions (>30%) with PHESGO were alopecia, nausea, diarrhea, anemia, and asthenia. ( 6.1 ) Metastatic Breast Cancer (based on intravenous pertuzumab ) The most common adverse reactions (> 30%) with pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Neoadjuvant and Adjuvant Treatment of Breast Cancer The safety of PHESGO was evaluated in an open-label, multicenter, randomized trial (FeDeriCa) conducted in 500 patients with HER2 overexpressing early breast cancer [see Clinical Studies (14.2) ] . Patients were randomized to receive either PHESGO (1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase/15 mL) followed every 3 weeks by a maintenance dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase/10 mL or the recommended dosages for intravenous pertuzumab and intravenous trastuzumab. Patients were randomized to receive 8 cycles of neoadjuvant chemotherapy with concurrent administration of 4 cycles of either PHESGO or intravenous pertuzumab and trastuzumab during cycles 5-8, followed by surgery. Following surgery, patients continued therapy with PHESGO alone or intravenous pertuzumab and trastuzumab (intravenous or subcutaneously administered) as treated prior to surgery, for an additional 14 cycles, to complete 18 cycles. The median duration of treatment for PHESGO was 24 weeks (range: 0-42 weeks). Serious adverse reactions occurred in 16% of patients who received PHESGO. Serious adverse reactions in > 1% of patients included febrile neutropenia (4%), neutropenic sepsis (1%), and neutrophil count decreased (1%). One fatal adverse reaction occurred in 1/248 (0.4%) of patients, which was due to acute myocardial infarction, and occurred prior to the start of HER2 targeted treatment with PHESGO. Adverse reactions resulting in permanent discontinuation of any study drug occurred in 8% of patients on the PHESGO arm. Adverse reactions which resulted in permanent discontinuation of PHESGO were ejection fraction decreased (1.2%), cardiac failure (0.8%), and pneumonitis/pulmonary fibrosis (0.8%). Dosage interruptions due to an adverse reaction occurred in 40% of patients who received PHESGO. Adverse reactions which required dosage interruption in > 1% of patients who received PHESGO included neutropenia (8%), neutrophil count decreased (4%), and diarrhea (7%). Table 3 summarizes the adverse reactions in FeDeriCa. Table 3: Adverse Reactions (≥5%) in Patients Who Received PHESGO in FeDeriCa Adverse Reactions PHESGO (n=248) Intravenous pertuzumab plus intravenous or subcutaneous trastuzumab (n=252) All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % Skin and subcutaneous tissue disorders Alopecia 77 0 71 0.4 Dry skin 15 0.4 13 0 Rash 16 0.4 21 0 Nail discoloration 9 0 6 0 Erythema 9 0 5 0 Dermatitis 7 0 6 0 Nail disorder 7 0 7 0.4 Palmar-plantar erythrodysaesthesia syndrome 6 0.8 5 0.4 Gastrointestinal disorders Nausea 60 2 61 1.6 Diarrhea 60 7 57 4.8...

Drug Interactions

7 DRUG INTERACTIONS Patients who receive anthracycline after stopping PHESGO may be at increased risk of cardiac dysfunction because of PHESGO's long washout period [see Clinical Pharmacology (12.3) ] . If possible, avoid anthracycline-based therapy for up to 7 months after stopping PHESGO. If anthracyclines are used, carefully monitor the patient's cardiac function.

Contraindications

4 CONTRAINDICATIONS PHESGO is contraindicated in patients with known hypersensitivity to pertuzumab, or trastuzumab, or hyaluronidase, or to any of its excipients. PHESGO is contraindicated in patients with known hypersensitivity to pertuzumab, or trastuzumab, or hyaluronidase, or to any of its excipients. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Pharmacovigilance Program There is a pregnancy pharmacovigilance program for PHESGO. If PHESGO is administered during pregnancy, or if a patient becomes pregnant while receiving PHESGO or within 7 months following the last dose of PHESGO, health care providers and patients should immediately report PHESGO exposure to Genentech at 1-888-835-2555. Risk Summary PHESGO can cause fetal harm when administered to a pregnant woman. In post-marketing reports, use of intravenous trastuzumab during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death (see Data ) . In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal deaths at clinically relevant exposures that were 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on C max (see Data ) . Apprise the patient of the potential risks to a fetus. There are clinical considerations if PHESGO is used during pregnancy or within 7 months prior to conception (see Clinical Considerations ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received PHESGO 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. Data Human Data In post-marketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied PHESGO (pertuzumab, trastuzumab, and hyaluronidase-zzxf) injection is a sterile, preservative-free, clear to opalescent, and colorless to slightly brownish solution in single-dose vials for subcutaneous administration supplied as each carton containing one single-dose vial: 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase/15 mL (80 mg, 40 mg, and 2,000 units/mL) (NDC 50242-245-01). 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase/10 mL (60 mg, 60 mg, 2,000 units/mL) (NDC 50242-260-01). Storage and Handling Store PHESGO vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.