Recommended dosing and administration for PHESGO

Step-by-step tutorial for preparing and administering  PHESGO

The purpose of this video is to help educate on how to properly administer PHESGO. For full information on dosing considerations, dose modifications and monitoring, and complete administration information, please review the PHESGO full Prescribing Information.

Indications

Early Breast Cancer 

PHESGO™ (pertuzumab, trastuzumab, and hyaluronidase-zzxf) 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 (EBC)
  • the adjuvant treatment of adult patients with HER2-positive early breast cancer (EBC) at high risk of recurrence

Select patients for therapy based on an FDA-approved companion diagnostic test.

Metastatic Breast Cancer 

PHESGO is indicated for use in combination with docetaxel for the treatment of adult patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Select patients for therapy based on an FDA-approved companion diagnostic test.

Important Safety Information

BOXED WARNINGS: Cardiomyopathy, Embryo-Fetal Toxicity, and Pulmonary Toxicity

  • PHESGO administration can result in subclinical and clinical cardiac failure. The incidence and severity was 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
  • 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
  • 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

Perform HER2 testing using FDA-approved tests by laboratories with demonstrated proficiency. 

Dosing schedules

  • Metastatic breast cancer: administer PHESGO by subcutaneous injection and docetaxel by intravenous infusion every 3 weeks until disease recurrence or unmanageable toxicity, whichever occurs first 
  • Neoadjuvant treatment: administer PHESGO by subcutaneous injection every 3 weeks and chemotherapy by intravenous infusion preoperatively for 3 to 6 cycles or until disease recurrence or unmanageable toxicity, whichever occurs first, as a part of a complete regimen for early breast cancer 
  • Adjuvant treatment: administer PHESGO by subcutaneous injection every 3 weeks and     chemotherapy by intravenous infusion postoperatively for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first, as a part of a complete regimen for early breast cancer

PHESGO is a fixed-dose, subcutaneous combination of pertuzumab, trastuzumab and hyaluronidase in a single vial. The following video will review key points on how to properly store, prepare, and administer PHESGO. 

On screen: Image of vial used for illustrative purposes only. 

Let’s start with the product itself.

PHESGO is a fixed-dose combination, which means that all patients receive the same dose, regardless of their weight. PHESGO has different dosage and administration instructions than IV PERJETA + trastuzumab, and subcutaneous trastuzumab when administered alone. Do not substitute PHESGO for or with PERJETA, trastuzumab, ado-trastuzumab emtansine, or fam-trastuzumab deruxtecan.

PHESGO comes in two formulations: 

The first formulation is a loading dose of 15 milliliters. This ready-to-use vial contains 1,200 milligrams of pertuzumab, 600 milligrams of trastuzumab, and 30,000 units of hyaluronidase.

The second formulation is a maintenance dose of 10 milliliters. This ready-to-use vial contains 600 milligrams of pertuzumab, 600 milligrams of trastuzumab, and 20,000 units of hyaluronidase.

PHESGO is supplied in sterile, preservative-free, single-dose vials for subcutaneous injection. Store PHESGO vials in the refrigerator at 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit) in the original carton to protect from light, until time of use. Do not freeze or shake the vials.

PREPARING THE PATIENT

There are a couple of points that can help a patient to prepare for the injection.

Consider asking the patient to wear loose clothing that will make it easy to access the thigh area. A skirt or loose shorts may be an option.

PREPARING THE INJECTION

Now it’s time to prepare the solution for the injection. Please follow your local or institutional guidelines for preparation.

When preparing for administering PHESGO, use the appropriate personal protective equipment, according to your local facility standards.

To prevent medication errors, it is important to check the vial labels to ensure the drug being prepared and administered is PHESGO.

Select the right dose, and check the expiration date. Inspect the vial for particulate matter and discoloration, whenever solution and container permit. PHESGO is clear to opalescent, and colorless to slightly brownish. Do not use if particulates or discoloration are present.

Both the initial and maintenance doses are ready to use for subcutaneous injection, and should not be diluted. 

Start by attaching a transfer needle to the syringe. Remove and discard the vial cap and wipe the vial stopper with an alcohol swab. Allow the stopper to dry naturally, and then, holding the syringe by the barrel, insert the transfer needle into the center of the vial.

Now, invert the vial and slowly pull back the plunger until you’ve withdrawn the contents of the vial. Discard any unused portion remaining in the vial.

Once the contents are withdrawn from the vial, remove the needle from the vial. Then remove the transfer needle from the syringe.

Label the syringe with the included peel-off sticker.

If the solution will not be injected right away, replace the transfer needle with a syringe closing cap. Do not attach a hypodermic needle until the time of administration to avoid needle clogging.

After filling the syringe, PHESGO can be stored in the refrigerator for up to 24 hours, and at room temperature for up to 4 hours.

On screen:

  • The syringe may be stored for up to 24 hours in the refrigerator (2°-8° C or 36°-46° F)
  • A maximum of 4 hours at room temperature (20°-25° C or 68°-77° F)
  • Avoid unnecessary storage

The solution should be administered at room temperature, so remove it from the fridge enough time in advance for it to warm up.

At the time of administration, detach the transfer needle or syringe stopper and discard, replacing it with a sterile injection needle.

The suitable injection needle for this solution is between 25 and 27 gauge and between 3/8 of an inch and 5/8 of an inch long.

PHESGO is now ready for injection. 

ADMINISTERING THE INJECTION

PHESGO should always be administered by a healthcare professional.

Ask the patient to sit back in a reclining chair or bed and to make the thigh area accessible. Be sure to arrange your chair at the right level so that your feet are flat on the floor and you are able sit up straight without twisting, bending, or reaching to administer the injection. You will be in this position for approximately 5 to 8 minutes, so be sure you are comfortable and in a position that you can maintain.

The injection site should be alternated between the left and right thigh only. It is never administered in the abdomen or intravenously. Do not split the dose between two syringes or between two sites of administration.

Each new injection should be given at least 1 inch, or 2.5 cm, from the previous site.

Choose an area of healthy skin that is not red, bruised, tender, or hard. During treatment with PHESGO, other subcutaneous medications should preferably be injected at different sites.

On screen:

  • Sanitize the area 

To perform the injection, pinch the skin of the thigh with one hand to create a fold. This makes it easier to get the injection into the subcutaneous tissue and not into the muscle tissue.

The dose should be administered at a rate of no more than 2 milliliters per minute, so you can expect the loading dose to take approximately 8 minutes to administer, while the maintenance doses will take approximately 5 minutes. 

The injection should be slowed or paused if the patient experiences a significant injection-related reaction. The injection should be discontinued immediately if the patient experiences a serious hypersensitivity reaction (for example, anaphylaxis). 

On screen:

  • Evaluate and monitor patient until resolution of signs/symptoms

The preparation and administration time presents a good opportunity to talk with the patient, to get an overall sense of their well-being and to discuss any concerns they may be having.

Once the full dose has been administered, wait briefly before removing the needle to minimize any potential leak back.

After the loading dose, the patient should be observed for a minimum of 30 minutes, for signs of hypersensitivity symptoms or administration-related reactions. After the maintenance doses, the patient should be observed for a minimum of 15 minutes. Make sure that medication to treat reactions, as well as emergency equipment, is available for immediate use.

For full information on dosing considerations, dose modifications and monitoring, and complete administration information, please review the PHESGO full prescribing information.

On screen: Visit PHESGO.com for Full Prescribing Information

Thank you for taking the time to watch this video and for all the work that you do for patients.

On screen: To learn more about administering PHESGO, or to schedule an educational in-service contact us at PhesgoSupport@gene.com.

Please continue watching for additional Important Safety Information.

Important Safety Information

Contraindications

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

Additional Important Safety Information

Cardiomyopathy and Cardiac Monitoring

  • PHESGO administration can result in subclinical and clinical cardiac failure. The incidence and severity was highest in patients receiving PHESGO with anthracycline-containing chemotherapy regimens
  • Discontinue PHESGO treatment in patients receiving adjuvant therapy and withhold PHESGO in patients with metastatic disease for clinically significant decrease in left ventricular function
  • Evaluate cardiac function prior to and during treatment. For adjuvant therapy, also evaluate cardiac function after completion of PHESGO
  • Monitor frequently for decreased left ventricular function during and after PHESGO treatment. Monitor more frequently if PHESGO is withheld for significant left ventricular cardiac dysfunction

Embryo-Fetal Toxicity

  • PHESGO can cause fetal harm when administered to a pregnant woman 
  • Verify the pregnancy status of females of reproductive potential prior to the initiation of PHESGO. Advise pregnant women and females of reproductive potential that exposure to PHESGO during pregnancy or within 7 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PHESGO
  • 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

Pulmonary Toxicity

  • PHESGO can cause serious and fatal pulmonary toxicity. These adverse reactions have been reported with intravenous trastuzumab
  • Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity

Exacerbation of Chemotherapy-Induced Neutropenia

  • PHESGO may exacerbate chemotherapy-induced neutropenia. In randomized controlled clinical trials with intravenous trastuzumab, Grade 3-4 neutropenia and febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone 

Hypersensitivity and Administration-Related Reactions

  • Severe administration-related reactions (ARRs), including hypersensitivity, anaphylaxis, and events with fatal outcomes, have been associated with intravenous pertuzumab and trastuzumab. Patients experiencing dyspnea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of a severe or of a fatal ARR 
  • In the FeDeriCa study, the incidence of hypersensitivity was 1.2% in the PHESGO arm. ARRs occurred in 21% of patients who received PHESGO. In the PHESGO arm, the most common administration-related reactions were injection site reaction (15%) and injection site pain (2%) 
  • Closely monitor patients during and for 30 minutes after the injection of initial dose and during and for 15 minutes following subsequent injections of maintenance dose of PHESGO. If a significant injection-related reaction occurs, slow down or pause the injection and administer appropriate medical therapies. Evaluate and carefully monitor patients until complete resolution of signs and symptoms 
  • Permanently discontinue treatment with PHESGO in patients who experience anaphylaxis or severe injection-related reactions. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. For patients experiencing reversible Grade 1 or 2 hypersensitivity reactions, consider pre-medication with an analgesic, antipyretic, or an antihistamine prior to readministration of PHESGO

Most Common Adverse Reactions

Early Breast Cancer

The most common adverse reactions (>30%) with PHESGO were alopecia, nausea, diarrhea, anemia, and asthenia.

Metastatic Breast Cancer (based on IV 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.

You are encouraged to report side effects to Genentech and the FDA. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety Information, including BOXED WARNINGS. 

Thank you.

Administration instructions

Important: PHESGO has different dosage and administration instructions than IV pertuzumab, IV trastuzumab, and subcutaneous trastuzumab when administered alone. Do not substitute PHESGO for or with PERJETA® (pertuzumab), trastuzumab, ado-trastuzumab emtansine, or fam-trastuzumab deruxtecan.1

PHESGO should be administered every 3 weeks1,2

Loading (initial) dose

1200 mg pertuzumab, 600 mg trastuzumab, 30,000 units hyaluronidase per 15 mL supplied in a single-dose, ready-to-use vial

Administer subcutaneously over approximately 8 minutes at a rate of no more than 2 mL/min

Observe for hypersensitivity or administration-related reactions:  minimum of 30 minutes*

NDC: 50242-245-01

Maintenance dose

600 mg pertuzumab, 600 mg trastuzumab, 20,000 units hyaluronidase per 10 mL supplied in a single-dose, ready-to-use vial

Administer subcutaneously over approximately 5 minutes at a rate of no more than 2 mL/min

Observe for hypersensitivity or administration-related reactions: minimum of 15 minutes*

NDC: 50242-260-01

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

PHESGO must always be administered by a healthcare professional.

PHESGO is for subcutaneous use ONLY in the thigh. Do NOT administer intravenously.

  • Do not split the dose between 2 syringes or between 2 sites of administration
  • Injection site should be alternated between the left and right thigh only
  • New injections should be given at least 1 inch from the previous site on healthy skin and never into areas where the skin is red, bruised, tender, or hard
  • During the treatment course with PHESGO, other subcutaneous medications should preferably be injected at different sites

Patients currently receiving IV PERJETA + trastuzumab can be transitioned to PHESGO if eligible.1

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) state that pertuzumab, trastuzumab, and hyaluronidase-zzxf injection for subcutaneous use (PHESGO) may be substituted anywhere that IV pertuzumab (PERJETA) + trastuzumab are given as part of systemic therapy for HER2+ breast cancer.†3

Pertuzumab, trastuzumab, and hyaluronidase-zzxf injection for subcutaneous use (PHESGO) has different dosing and administration instructions compared to the intravenous products.

Additional dosing considerations and dose modifications

Assessment of HER2 protein overexpression and/or HER2 gene amplification should be performed using FDA-approved tests specific for breast cancers by laboratories with demonstrated proficiency.

  • In patients receiving an anthracycline-based regimen for EBC, administer PHESGO following completion of the anthracycline
  • In patients receiving PHESGO for EBC with docetaxel or paclitaxel, administer docetaxel or paclitaxel after PHESGO
  • In patients receiving PHESGO for MBC with docetaxel, administer docetaxel after PHESGO

<6 weeks since last dose of IV PERJETA + trastuzumab
START PHESGO with maintenance dose

≥6 weeks since last dose of IV PERJETA + trastuzumab
START PHESGO with loading dose

  • In patients receiving IV PERJETA + trastuzumab with <6 weeks since their last dose, administer PHESGO as a maintenance dose of 600 mg, 600 mg, 20,000 units/10 mL and every 3 weeks for subsequent administrations
  • In patients receiving IV PERJETA + trastuzumab with ≥6 weeks since their last dose, administer PHESGO as an initial dose of 1,200 mg, 600 mg, 30,000 units/15 mL, followed by a maintenance dose of 600 mg, 600 mg, 20,000 units/10 mL every 3 weeks for subsequent administrations
  • In the PHranceSCa trial, patients were monitored for 30 minutes after their first dose of PHESGO, regardless of whether a loading dose was required. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use
  • If the time between 2 sequential injections is less than 6 weeks, do not wait until the next planned dose. The maintenance dose of 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase should be administered
  • If the time between 2 sequential injections is 6 weeks or more, the initial dose of 1200 mg pertuzumab/600 mg trastuzumab/30,000 units hyaluronidase should be re-administered, followed every 3 weeks thereafter by a dose of 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase
  • No dose adjustments for PHESGO are required for patient body weight or for concomitant chemotherapy regimen
  • For chemotherapy dose modification, see relevant prescribing information
  • If patient experiences a significant injection-related reaction, slow down or pause the injection and administer appropriate medical therapies. Evaluate and carefully monitor patients until complete resolution of signs and symptoms
  • If patient experiences a serious hypersensitivity reaction (e.g., anaphylaxis), discontinue injection immediately

Assess left ventricular ejection fraction (LVEF) prior to initiation of PHESGO and at regular intervals during treatment.

Guidance for LVEF monitoring

For patients receiving anthracycline-based chemotherapy, a LVEF of ≥50% is required after completion of anthracyclines, before starting PHESGO.

Monitor LVEF prior to initiation and then every ~12 weeks in MBC and EBC (once during neoadjuvant therapy).

If after a repeat assessment within approximately 3 weeks, the LVEF has not improved, has declined further, and/or the patient is symptomatic, permanently discontinue PHESGO.

    • PHESGO Prescribing Information. Genentech, Inc. 2020.

      PHESGO Prescribing Information. Genentech, Inc. 2020.

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V6.2020. © National Comprehensive Cancer Network, Inc, 2020. All rights reserved. Accessed September 10, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V6.2020. © National Comprehensive Cancer Network, Inc, 2020. All rights reserved. Accessed September 10, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

    Important Safety Information & Indications

    Indications

    Early Breast Cancer

    PHESGO® (pertuzumab, trastuzumab, and hyaluronidase-zzxf) 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 (EBC)
    • the adjuvant treatment of adult patients with HER2-positive early breast cancer (EBC) at high risk of recurrence

    Select patients for therapy based on an FDA-approved companion diagnostic test.

    Metastatic Breast Cancer

    PHESGO is indicated for use in combination with docetaxel for the treatment of adult patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

    Select patients for therapy based on an FDA-approved companion diagnostic test.

    BOXED WARNINGS: Cardiomyopathy, Embryo-Fetal Toxicity, and Pulmonary Toxicity

    • PHESGO administration can result in subclinical and clinical cardiac failure. The incidence and severity was 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
    • 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

    • 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

    Contraindications

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

    Additional Important Safety Information

    Cardiomyopathy

    • PHESGO administration can result in subclinical and clinical cardiac failure. The incidence and severity was highest in patients receiving PHESGO with anthracycline-containing chemotherapy regimens. An increased incidence of left ventricular ejection fraction (LVEF) decline has been observed in patients treated with intravenous pertuzumab, intravenous trastuzumab, and docetaxel

    • PHESGO can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death

    • PHESGO can also cause asymptomatic decline in LVEF

    • Patients who receive anthracycline after stopping PHESGO may also be at increased risk of cardiac dysfunction

    • Discontinue PHESGO treatment in patients receiving adjuvant therapy and withhold PHESGO in patients with metastatic disease for clinically significant decrease in left ventricular function

    Cardiac Monitoring

    • Evaluate cardiac function prior to and during treatment. For adjuvant breast cancer therapy, also evaluate cardiac function after completion of PHESGO

    • Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan

    • Monitor frequently for decreased left ventricular function during and after PHESGO treatment

    • Monitor more frequently if PHESGO is withheld for significant left ventricular cardiac dysfunction

    Embryo-Fetal Toxicity

    • 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. In an animal reproduction study, administration of intravenous pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal death at exposures 2.5 to 20 times the exposure in humans at the recommended dose, based on Cmax

    • Verify the pregnancy status of females of reproductive potential prior to the initiation of PHESGO. Advise pregnant women and females of reproductive potential that exposure to PHESGO during pregnancy or within 7 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PHESGO

    • 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

    Pulmonary Toxicity

    • PHESGO can cause serious and fatal pulmonary toxicity. These adverse reactions have been reported with intravenous trastuzumab

    • Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity

    Exacerbation of Chemotherapy-Induced Neutropenia

    • PHESGO may exacerbate chemotherapy-induced neutropenia. In randomized controlled clinical trials with intravenous trastuzumab, Grade 3-4 neutropenia and febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not

    Hypersensitivity and Administration-Related Reactions

    • Severe administration-related reactions (ARRs), including hypersensitivity, anaphylaxis, and events with fatal outcomes, have been associated with intravenous pertuzumab and trastuzumab. Patients experiencing dyspnea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of a severe or of a fatal ARR

    • In the FeDeriCa study the incidence of hypersensitivity was 1.2% in the PHESGO arm. ARRs occurred in 21% of patients who received PHESGO. In the PHESGO arm, the most common ARRs were injection site reaction (15%) and injection site pain (2%).

    • Closely monitor patients during and for 30 minutes after the injection of initial dose and during and for 15 minutes following subsequent injections of maintenance dose of PHESGO. If a significant injection-related reaction occurs, slow down or pause the injection and administer appropriate medical therapies. Evaluate and carefully monitor patients until complete resolution of signs and symptoms

    • Permanently discontinue treatment with PHESGO in patients who experience anaphylaxis or severe injection-related reactions. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. For patients experiencing reversible Grade 1 or 2 hypersensitivity reactions, consider pre-medication with an analgesic, antipyretic, or an antihistamine prior to readministration of PHESGO

    Most Common Adverse Reactions

    Early Breast Cancer

    The most common adverse reactions (>30%) with PHESGO were alopecia, nausea, diarrhea, anemia, and asthenia.

    Metastatic Breast Cancer (based on IV 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.

    You are encouraged to report side effects to Genentech and the FDA. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

    Please see full Prescribing Information for additional Important Safety Information, including BOXED WARNINGS.