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PHESGO side effects and safety profile

FeDeriCa safety data
PHranceSCa safety data

Comparable safety was observed in FeDeriCa between both arms1

Summary of adverse reactions (ARs) occurring in ≥15% of patients who received PHESGO1

  All Grades (%) Grades 3-4 (%)
  PHESGO (n=248) IV PERJETA® (pertuzumab) + IV/SC trastuzumab (n=252) PHESGO (n=248) IV PERJETA + IV/SC trastuzumab (n=252)
Alopecia 77 71 0 0.4
Nausea 60 61 2 1.6
Diarrhea 60 57 7 4.8
Anemia 36 43 1.6 4.4
Asthenia 31 32 0.4 2.4
Fatigue 29 24 2 2
Stomatitis 25 24 0.8 0.8
Myalgia 25 19 0.4 0.4
Arthralgia 24 28 0 0.4
Constipation 22 21 0 0
Neutropenia 22 27 14 14
Vomiting 20 19 0.8 1.2
Radiation skin injury 19 19 0.4 0.4
Dysgeusia 17 14 0 0
Headache 17 25 0 0.8
Decreased appetite 17 19 0.8 0.4
Insomnia 17 13 0 0.4
Peripheral sensory neuropathy 16 14 0.8 0.4
Rash 16 21 0.4 0
Dry skin 15 13 0.4 0
Mucosal inflammation 15 20 0.8 1.2
Injection site reaction* 15 0.8 0 0
Cough 15 13 0.4 0

*An injection site reaction was defined as a local reaction.2

Understanding injection site reactions (ISRs) in the FeDeriCa trial1-3

  • ISRs in FeDeriCa were all mild to moderate (Grades 1-2)
  • Mild ISRs were characterized by tenderness with or without associated symptoms like warmth, erythema, or itching
  • Moderate ISRs were characterized by pain, lipodystrophy, edema, or phlebitis

Serious ARs occurring in patients receiving PHESGO1

  • Serious ARs occurred in 16% of patients who received PHESGO
  • Serious ARs 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

ARs resulting in permanent discontinuation of any study drug occurred in 8% of patients in the PHESGO arm. ARs which resulted in permanent discontinuation of PHESGO were ejection fraction decreased (1.2%), cardiac failure (0.8%), and pneumonitis/pulmonary fibrosis (0.8%).1

Dosage interruptions (of any study drug) due to an AR occurred in 40% of patients who received PHESGO. ARs which required dosage interruption (of any study drug) in >1% of patients who received PHESGO included neutropenia (8%), neutrophil count decreased (4%), and diarrhea (7%).1

SC=subcutaneous.

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Safety data from the PHranceSCa trial†2,4

Graph showing safety data when patients switched between PHESGO and PERJETA + trastuzumab

AR rates before and after switching treatment2,4:

  • From IV PERJETA + trastuzumab to PHESGO: 78% → 73%
  • From PHESGO to IV PERJETA + trastuzumab: 78% → 64%

During the crossover period, serious ARs were reported in 2 patients (1.3%) receiving  PHESGO and in 6 patients (3.8%) receiving IV PERJETA + trastuzumab; Grade ≥3 ARs were reported in 4 patients (2.5%) receiving PHESGO and in 6 patients (3.8%) receiving IV PERJETA + trastuzumab. There were no Grade 4 or 5 ARs reported during the study at the clinical cut-off date. More injection site reactions were observed with PHESGO (all Grade 1 or 2). There were no discontinuations due to local injection site reactions with PHESGO.2,4

†Data are based on the primary analysis with a CCOD of February 24, 2020. As of the CCOD, all 160 patients had completed all 6 cycles of the crossover period.1,5

Limitations of data: These safety analyses are descriptive only.

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PHESGO dosing and administration

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    • PHESGO Prescribing Information. Genentech, Inc. 2020.

      PHESGO Prescribing Information. Genentech, Inc. 2020.

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.

    • National Cancer Institute. National Institutes of Health. U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, June 14, 2010. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed September 30, 2020.

      National Cancer Institute. National Institutes of Health. U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, June 14, 2010. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed September 30, 2020.

    • O’Shaughnessy J, Sousa S, Cruz J, et al. Patient (pt) preference for the pertuzumab–trastuzumab fixed-dose combination for subcutaneous use (PH FDC SC) in HER2-positive early breast cancer (EBC): Primary analysis of the open-label, randomised crossover PHranceSCa study. https://medically.roche.com/global/en/asset-viewer.eeb4fcc7-b0b5-43d5-9b9a-8f4445f7424f.qr.html?cid=slpsxx2009onbresmo2020. Accessed September 30, 2020.

      O’Shaughnessy J, Sousa S, Cruz J, et al. Patient (pt) preference for the pertuzumab–trastuzumab fixed-dose combination for subcutaneous use (PH FDC SC) in HER2-positive early breast cancer (EBC): Primary analysis of the open-label, randomised crossover PHranceSCa study. https://medically.roche.com/global/en/asset-viewer.eeb4fcc7-b0b5-43d5-9b9a-8f4445f7424f.qr.html?cid=slpsxx2009onbresmo2020. Accessed September 30, 2020.

    • ClinicalTrials.gov. A study to evaluate patient preference and satisfaction of subcutaneous administration of the fixed-dose combination of pertuzumab and trastuzumab in participants with HER2-positive early breast cancer (PHranceSCa). https://clinicaltrials.gov/ct2/show/NCT03674112. Accessed May 7, 2020.

      ClinicalTrials.gov. A study to evaluate patient preference and satisfaction of subcutaneous administration of the fixed-dose combination of pertuzumab and trastuzumab in participants with HER2-positive early breast cancer (PHranceSCa). https://clinicaltrials.gov/ct2/show/NCT03674112. Accessed May 7, 2020.

    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.