SELECT NEOADJUVANT DOSING AND ADMINISTRATION

Patient selection

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.¹

Neoadjuvant eligibility

To begin PERJETA and Herceptin^® (trastuzumab)-based therapy in the neoadjuvant setting, patients must have HER2+ breast cancer with locally advanced, inflammatory, or early stage breast cancer (either node-positive or tumor size >2 cm).¹

Please see the full Prescribing Information for complete dosing and administration, including dose considerations, dose modifications, preparation, storage, and handling. You can also download the PERJETA Dosing & Administration Guide.

LEARN ABOUT PERJETA DOSING & ADMINISTRATION

IN THE ADJUVANT SETTING

Patients who begin PERJETA and Herceptin in the neoadjuvant setting should continue to receive PERJETA and Herceptin every 3 weeks for a total of 1 year (up to 18 cycles), or until disease recurrence or unmanageable toxicity, whichever occurs first.¹

Continuing PERJETA in the adjuvant setting

PERJETA neoadjuvant and adjuvant treatment regimens

*Or until disease recurrence or unmanageable toxicity, whichever comes first.

Recommended dosing

PERJETA and Herceptin are administered every 3 weeks¹

PERJETA is a fixed dose, regardless of body weight. Administer 840 mg loading dose, 420 mg for subsequent cycles; Herceptin dosing: 8 mg/kg loading dose, 6 mg/kg for subsequent cycles.

Dosing considerations

Dose sequencing¹

PERJETA, Herceptin, and taxanes should be administered sequentially
- PERJETA and Herceptin can be given in any order, and taxane should be administered after PERJETA and Herceptin
In patients receiving an anthracycline-based regimen, PERJETA and Herceptin should be administered following completion of the anthracycline
An observation period of 30 to 60 minutes is recommended after each PERJETA infusion and before commencement of any subsequent infusion of Herceptin or chemotherapy

If a delayed or missed dose of PERJETA occurs¹

Dose interruption or discontinuation of treatment¹

PERJETA should be discontinued if Herceptin treatment is discontinued
Dose reductions are not recommended for PERJETA
For chemotherapy dose modifications, see their respective prescribing information
If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies
- The infusion should be discontinued immediately if the patient experiences a serious hypersensitivity reaction

Neoadjuvant chemotherapy regimens¹

4 preoperative cycles of PERJETA in combination with Herceptin and docetaxel,^† followed by 3 postoperative cycles of FEC,^‡ as given in NeoSphere
3 or 4 preoperative cycles of FEC^‡ alone, followed by 3 or 4 preoperative cycles of PERJETA in combination with docetaxel^† and Herceptin, as given in TRYPHAENA and BERENICE, respectively
6 preoperative cycles of PERJETA in combination with docetaxel,^† carboplatin,^§ and Herceptin (escalation of docetaxel above 75 mg/m² is not recommended), as given in TRYPHAENA
4 preoperative cycles of ddAC alone,^‖ followed by 4 preoperative cycles of PERJETA in combination with paclitaxel^¶ and Herceptin, as given in BERENICE

^†Docetaxel dosing: 75 mg/m², which could be escalated to 100 mg/m² if initial dose was well-tolerated (escalation of docetaxel above 75 mg/m² is not recommended when administered with carboplatin as in TRYPHAENA).
^‡FEC dosing in NeoSphere: 5-fluorouracil (600 mg/m²), epirubicin (90 mg/m²), and cyclophosphamide (600 mg/m²); FEC dosing in TRYPHAENA and BERENICE: 5-fluorouracil (500 mg/m²), epirubicin (100 mg/m²), and cyclophosphamide (600 mg/m²).
^§Carboplatin dosing: AUC 6.
^‖ddAC dosing: doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) every 2 weeks for 4 cycles with GCSF support.
^¶Paclitaxel dosing: 80 mg/m².
ddAC=dose-dense doxorubicin and cyclophosphamide; FEC=5-fluorouracil, epirubicin, and cyclophosphamide.

Patient monitoring¹

Left ventricular ejection fraction (LVEF)
Assess LVEF prior to initiation of PERJETA and at regular intervals during treatment to ensure that LVEF is within normal limits, as indicated below. If LVEF declines and has not improved, or has declined further at the subsequent assessment, discontinuation of PERJETA and trastuzumab should be strongly considered.

Dose modifications for left ventricular dysfunction in EBC

Dose modifications for left ventricular dysfunction (EBC)

^#For patients receiving anthracycline-based chemotherapy, an LVEF ≥50% is required after completion of anthracyclines, before starting PERJETA and Herceptin.

Cardiac monitoring

Early Breast Cancer

PERJETA^® (pertuzumab) is indicated for use in combination with Herceptin^® (trastuzumab) and chemotherapy for

the 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 (EBC)

the adjuvant treatment of patients with HER2-positive early breast cancer (EBC) at high risk of recurrence

BOXED WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity

PERJETA can result in subclinical and clinical cardiac failure manifesting as decreased left ventricular ejection fraction (LVEF) and congestive heart failure (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 C_max
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 pharmacovigilance program for PERJETA. 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, healthcare providers and patients should immediately report PERJETA exposure to Genentech at 1-888-835-2555

Most Common Adverse Reactions

Neoadjuvant Treatment of Breast Cancer

The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel administered for 4 cycles were alopecia, neutropenia, diarrhea, and nausea. 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 administered for 3 cycles following 3 cycles of FEC were diarrhea, nausea, alopecia, neutropenia, vomiting, and fatigue. The most common NCI-CTCAE v3.0 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 TCH administered for 6 cycles were diarrhea, alopecia, neutropenia, nausea, fatigue, vomiting, anemia, and thrombocytopenia. The most common NCI-CTCAE v3.0 Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, anemia, leukopenia, diarrhea, thrombocytopenia, vomiting, fatigue, alanine aminotransferase (ALT) increased, hypokalemia, and hypersensitivity

The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and paclitaxel administered for 4 cycles following 4 cycles of ddAC were nausea, diarrhea, alopecia, fatigue, constipation, peripheral neuropathy, and headache. The most common Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, neutrophil count decreased, white blood cell count decreased, anemia, diarrhea, peripheral neuropathy, ALT increased, and nausea

The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel administered for 4 cycles following 4 cycles of FEC were diarrhea, nausea, alopecia, asthenia, constipation, fatigue, mucosal inflammation, vomiting, myalgia, and anemia. The most common Grades 3-4 adverse reactions (>2%) were febrile neutropenia, diarrhea, neutropenia, neutrophil count decreased, stomatitis, fatigue, vomiting, mucosal inflammation, neutropenic sepsis, and anemia

Adjuvant Treatment of Breast Cancer

The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and chemotherapy were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting. The most common Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, diarrhea, neutrophil count decreased, anemia, white blood cell count decreased, leukopenia, fatigue, nausea, and stomatitis

The incidence of diarrhea, all Grades, was higher when chemotherapy was administered with targeted therapy (61% in the PERJETA-treated group vs 34% in the placebo-treated group) and was higher when administered with non–anthracycline-based therapy (85% in the PERJETA-treated group vs 62% in the placebo-treated group) than with anthracycline-based therapy (67% in the PERJETA-treated group vs 41% in the placebo-treated group). The incidence of diarrhea during the period that targeted therapy was administered without chemotherapy was 18% in the PERJETA-treated group vs 9% in the placebo-treated group. The median duration of all Grades diarrhea was 8 days for the PERJETA-treated group vs. 6 days for the placebo-treated group. The median duration of Grade ≥3 diarrhea was 20 days for the PERJETA-treated group vs. 8 days for the placebo-treated group. More patients required hospitalization for diarrhea as a serious adverse event in the PERJETA-treated group (2.4%) than in the placebo-treated group (0.7%)

Metastatic Breast Cancer

The most common adverse reactions (>30%) seen with PERJETA in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. The most common NCI-CTCAE v3.0 Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, leukopenia, diarrhea, peripheral neuropathy, anemia, asthenia, and fatigue

SELECT NEOADJUVANT DOSING AND ADMINISTRATION

Patient selection

Neoadjuvant eligibility

LEARN ABOUT PERJETA DOSING & ADMINISTRATION

IN THE ADJUVANT SETTING

Recommended dosing

Dosing considerations

Neoadjuvant chemotherapy regimens¹

Patient monitoring¹

Reference

Important Safety Information/Indications

Indications:

Early Breast Cancer

Metastatic Breast Cancer

BOXED WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity

Additional Important Safety Information

Most Common Adverse Reactions

SELECT NEOADJUVANT DOSING AND ADMINISTRATION

Patient selection

Neoadjuvant eligibility

LEARN ABOUT PERJETA DOSING & ADMINISTRATION

IN THE ADJUVANT SETTING

Recommended dosing

Dosing considerations

Neoadjuvant chemotherapy regimens1

Patient monitoring1

Important Safety Information/Indications

Indications:

Early Breast Cancer

Metastatic Breast Cancer

BOXED WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity

Additional Important Safety Information

Most Common Adverse Reactions

Coming Soon

Neoadjuvant chemotherapy regimens¹

Patient monitoring¹