| NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend a pertuzumab (PERJETA®) and trastuzumab (Herceptin®) combination-based neoadjuvant regimen as an option for the treatment of HER2-positive (HER2+) early-stage breast cancer (category 2A)1 |
|
|
| Based upon lower-level evidence, there is uniform National Comprehensive Cancer Network® (NCCN®) consensus that the intervention is appropriate (category 2A)1 |
| Could your patients with HER2+ early-stage breast cancer be eligible for PERJETA-based neoadjuvant treatment? |
|
|
| Indication |
| PERJETA® (pertuzumab) is a HER2/neu receptor antagonist indicated for use in combination with Herceptin® (trastuzumab) and docetaxel 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. This indication is based on demonstration of an improvement in pathological complete response rate. No data are available demonstrating improvement in event-free survival or overall survival. |
| Limitations of Use: |
| • |
The safety of PERJETA as part of a doxorubicin‑containing regimen has not been established |
| • |
The safety of PERJETA administered for greater than 6 cycles for early breast cancer has not been established |
|
|
|
|
| Neoadjuvant PERJETA eligibility1-3 |
| Stage |
Tumor size (cm) |
NCCN Guidelines® recommended |
| IIA |
>2 but ≤5 |
 |
| IIB |
>5 |
|
| IIIB |
Any size with direct extension to chest wall or skin |
|
|
| Stage |
Tumor size (cm) |
NCCN Guidelines recommended |
| IB |
No evidence of tumor or ≤2 |
|
| IIA |
No evidence of tumor or ≤2 |
|
| IIB |
>2 but ≤5 |
|
| IIIA |
No evidence of tumor, or tumor of any size |
|
| IIIB |
Any size with direct extension to chest wall or skin |
|
| IIIC |
Any size |
|
|
| 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 |
|
| Please see additional select Important Safety Information throughout, and the accompanying full Prescribing Information, including Boxed WARNINGS. |
| Learn more about a neoadjuvant treatment approach with PERJETA |
|
|
| 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 |
| – |
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, left ventricular dysfunction, which includes symptomatic left ventricular systolic dysfunction (LVSD) (congestive heart failure) and decreases in left ventricular ejection fraction (LVEF), occurred in 4.4% of patients in the PERJETA-treated group and in 8.3% of patients in the placebo-treated group |
| • |
In Study 2, for patients receiving neoadjuvant treatment, the incidence of LVSD was higher in PERJETA-treated groups than in the trastuzumab and docetaxel group. An increased incidence of LVEF declines was observed in patients treated with PERJETA in combination with trastuzumab and docetaxel. In the overall treatment period, LVEF decline >10% and a drop to less than 50% occurred in 1.9% of patients treated with neoadjuvant trastuzumab and docetaxel as compared to 8.4% of patients treated with neoadjuvant PERJETA in combination with trastuzumab and docetaxel |
| • |
In Study 3, for patients receiving neoadjuvant treatment, in the overall treatment period, LVEF decline >10% and a drop to less than 50% occurred in 6.9% of patients treated with PERJETA plus trastuzumab and FEC followed by PERJETA plus trastuzumab and docetaxel, in 16.0% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC, and in 10.5% of patients treated with PERJETA in combination with TCH |
| • |
Assess LVEF prior to initiation of PERJETA and at regular intervals (eg, every 3 months in the metastatic setting and every 6 weeks in the neoadjuvant 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 trastuzumab and repeat LVEF assessment within approximately 3 weeks. Discontinue PERJETA and trastuzumab if LVEF has not improved or has declined further |
|
| Infusion-Associated Reactions |
| • |
PERJETA has been associated with infusion reactions |
| • |
In Study 1, 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 |
| • |
In Study 2 and Study 3, PERJETA was administered on the same day as the other study treatment drugs. Infusion reactions were consistent with those observed in Study 1, with a majority of reactions being National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE v3.0) Grades 1-2 |
| • |
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 reactions was 2.0% and 2.5%, respectively, according to NCI-CTCAE (version 3) |
| • |
In Study 2 and Study 3, hypersensitivity/anaphylaxis events were consistent with those observed in Study 1 |
| • |
Patients should be observed closely for hypersensitivity reactions. Severe hypersensitivity, including anaphylaxis, has been observed in clinical trials of PERJETA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use |
|
| 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 |
| Neoadjuvant Treatment of Breast Cancer |
| • |
The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel were alopecia, diarrhea, nausea, and neutropenia. The most common NCI-CTCAE v3.0 Grades 3‑4 adverse reactions (>2%) were neutropenia, febrile neutropenia, leukopenia, and diarrhea |
| • |
The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel when given for 3 cycles following 3 cycles of FEC were fatigue, alopecia, diarrhea, nausea, vomiting, and neutropenia. The most common NCI-CTCAE (version 3) Grades 3‑4 adverse reactions (>2%) were neutropenia, leukopenia, febrile neutropenia, diarrhea, left ventricular dysfunction, anemia, dyspnea, nausea, and vomiting |
| • |
The most common adverse reactions (>30%) with PERJETA in combination with docetaxel, carboplatin, and trastuzumab (TCH) for 6 cycles were fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, and anemia. The most common NCI-CTCAE (version 3) Grades 3‑4 adverse reactions (>2%) were neutropenia, febrile neutropenia, anemia, leukopenia, diarrhea, thrombocytopenia, vomiting, fatigue, ALT increased, hypokalemia, and hypersensitivity |
|
| 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. |
|
|
|
|
