PERJETA (pertuzumab)

Important Safety Information

Boxed WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity

  • PERJETA administration can result in subclinical and clinical cardiac failure manifesting as decreased LVEF and CHF. Evaluate cardiac function prior to and during treatment. Discontinue PERJETA treatment for a confirmed clinically significant decrease in left ventricular function
  • Exposure to PERJETA can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception

Additional Important Safety Information

  • PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients
  • PERJETA has been associated with infusion and hypersensitivity reactions/anaphylaxis
  • Detection of HER2 protein overexpression is necessary for selection of patients appropriate for PERJETA therapy
  • In metastatic breast cancer, the most common adverse reactions (>30%) seen with PERJETA in combination with Herceptin and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy

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 additional select Important Safety Information throughout, and the accompanying full Prescribing Information, including Boxed WARNINGS.

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CLEOPATRA AR Profile

PERJETA + Herceptin (trastuzumab) + docetaxel

CLEOPATRA Adverse Reaction (AR) Profile

Most Common Adverse Reactions: All Grades (>30%) or Grades 3-4 (>2%)1
Placebo+Herceptin+docetaxel (n=397)PERJETA+Herceptin+docetaxel (n=407)
All Grades, %Grades 3-4, %All Grades, %Grades 3-4, %
Diarrhea46.35.066.87.9
Alopecia60.50.360.90.0
Neutropenia49.645.852.848.9
Nausea41.60.542.31.2
Fatigue36.83.337.62.2
Rash24.20.833.70.7
Neuropathy peripheral33.82.032.43.2
Febrile neutropenia7.67.313.813.0
Leukopenia20.414.618.212.3
Anemia18.93.523.12.5
Asthenia30.21.526.02.5

Overall discontinuation rate of all study treatments due to adverse reactions in each treatment arm1:

  • 6.1% for PERJETA + Herceptin + docetaxel
  • 5.3% for placebo + Herceptin + docetaxel
  • Adverse reactions were reported less frequently after discontinuation of docetaxel treatment1
    • After docetaxel treatment was stopped, all adverse reactions in the PERJETA-treated group occurred in <10% of patients with the exception of diarrhea (19.1%), upper respiratory tract infection (12.8%), rash (11.7%), headache (11.4%), and fatigue (11.1%)

Select adverse reaction presentation

Febrile neutropenia
  • An increased incidence of febrile neutropenia was observed for Asian patients in both treatment arms compared with patients of other races and from other geographic regions1
    • Among Asian patients, the incidence of febrile neutropenia was higher in the PERJETA-treated group (26%) compared with the control group (12%)1
    • In patients from other geographic regions, the incidence of febrile neutropenia was 8.5% in the PERJETA-based arm and 5.6% in the Herceptin + docetaxel arm2
    • After docetaxel treatment was stopped, no instances of febrile neutropenia were reported in either treatment arm2
    • Use of granulocyte colony stimulating factor (G-CSF) was allowed for the treatment of febrile neutropenia and as prophylaxis; however, docetaxel dose reductions were the preferred measure for prevention of febrile neutropenia in subsequent cycles2
Diarrhea
  • The majority of diarrhea episodes occurred during the first 3 cycles of treatment2
    • The incidence of diarrhea was higher in the PERJETA-containing arm, a trend that persisted for Grade 1-2 severity following docetaxel discontinuation
    • For patients experiencing diarrhea, early intervention with loperamide was recommended

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References

  1. PERJETA Prescribing Information. Genentech, Inc. 2016.
  2. Baselga J, Cortés J, Im S-A, et al. Adverse events with pertuzumab and trastuzumab: evolution during treatment with and without docetaxel in CLEOPATRA. Poster presented at: 48th Annual Meeting of the American Society of Clinical Oncology (ASCO); June 1-5, 2012; Chicago, IL.

Indication

PERJETA® (pertuzumab) is a HER2/neu receptor antagonist indicated in combination with Herceptin® (trastuzumab) and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Important Safety Information

Boxed WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity

  • PERJETA administration can result in subclinical and clinical cardiac failure manifesting as decreased LVEF and CHF. Evaluate cardiac function prior to and during treatment. Discontinue PERJETA treatment for a confirmed clinically significant decrease in left ventricular function
  • Exposure to PERJETA can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception
    • Based on its mechanism of action and findings in animal studies, PERJETA can cause fetal harm when administered to a pregnant woman. PERJETA is a HER2/neu receptor antagonist. Cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported with use of another HER2/neu receptor antagonist (trastuzumab) during pregnancy. 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 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 PERJETA. Advise pregnant women and females of reproductive potential that exposure to PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm, including embryo-fetal death or birth defects. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PERJETA in combination with trastuzumab

    • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PERJETA during pregnancy. Encourage women who receive PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception, to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/
    • If PERJETA is administered during pregnancy, or if a patient becomes pregnant while receiving PERJETA or within 7 months following the last dose of PERJETA in combination with trastuzumab, health care providers and patients should immediately report PERJETA exposure to Genentech at 1-888-835-2555

Additional Important Safety Information

PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients.

Left Ventricular Dysfunction (LVD)
  • In Study 1, for patients with MBC, PERJETA in combination with Herceptin and docetaxel was not associated with increases in the incidence of symptomatic left ventricular systolic dysfunction (LVSD) or decreases in left ventricular ejection fraction (LVEF) compared with placebo in combination with Herceptin and docetaxel

  • Left ventricular dysfunction occurred in 4.4% of patients in the PERJETA-treated group and in 8.3% of patients in the placebo-treated group

  • Symptomatic LVSD (congestive heart failure) occurred in 1.0% of patients in the PERJETA-treated group and in 1.8% of patients in the placebo-treated group

  • Patients who have received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of decreased LVEF
  • Assess LVEF prior to initiation of PERJETA and at regular intervals (eg, every 3 months in the metastatic setting) during treatment to ensure that LVEF is within your institution’s normal limits
  • If LVEF is <45%, or is 45% to 49% with a 10% or greater absolute decrease below the pretreatment value, withhold PERJETA and Herceptin and repeat LVEF assessment within approximately 3 weeks. Discontinue PERJETA and Herceptin if LVEF has not improved or has declined further, unless benefits for the individual patient outweigh the risks

Infusion-Associated Reactions
  • PERJETA has been associated with infusion reactions
  • In Study 1, for patients with MBC, on the first day, when only PERJETA was administered, the overall frequency of infusion reactions was 13.0% in the PERJETA-treated group and 9.8% in the placebo-treated group, with the majority being mild to moderate. The most common infusion reactions (≥1.0%) were pyrexia, chills, fatigue, headache, asthenia, hypersensitivity, and vomiting

  • During the second cycle, when all drugs were administered on the same day, the most common infusion reactions in the PERJETA-treated group (≥1.0%) were fatigue, dysgeusia, hypersensitivity, myalgia, and vomiting
  • Observe patients closely for 60 minutes after the first infusion and for 30 minutes after subsequent infusions of PERJETA. If a significant infusion reaction occurs, slow or interrupt the 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
Hypersensitivity Reactions/Anaphylaxis
  • In Study 1, the overall frequency of hypersensitivity/anaphylaxis reactions was 10.8% in the PERJETA-treated group and 9.1% in the placebo-treated group. The incidence of Grades 3-4 hypersensitivity/anaphylaxis reactions was 2.0% in the PERJETA-treated group and 2.5% in the placebo-treated group according to NCI‑CTCAE (version 3). Overall, 4 patients in PERJETA-treated group and 2 patients in the placebo-treated group experienced anaphylaxis
  • Patients should be observed closely for hypersensitivity reactions. Severe hypersensitivity, including anaphylaxis, has been observed in clinical trials with treatment of PERJETA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients
HER2 Testing
  • Detection of HER2 protein overexpression is necessary for selection of patients appropriate for PERJETA therapy because these are the only patients studied and for whom benefit has been shown
Most Common Adverse Reactions

In MBC, the most common adverse reactions (>30%) seen with PERJETA in combination with Herceptin and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. The most common NCI-CTCAE (version 3) Grade 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, leukopenia, diarrhea, peripheral neuropathy, anemia, asthenia, and fatigue.

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 additional select Important Safety Information throughout, and the accompanying full Prescribing Information, including Boxed WARNINGS.