Dosing and uses of Perjeta (pertuzumab)
Metastatic Breast Cancer
Indicated in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer in patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease
Initial dose: 840 mg IV infusion over 60 min, THEN 420 mg IV infusion over 30-60 min q3wk
Trastuzumab: 8 mg/kg IV infusion over 90 min initially, then 6 mg/kg IV infusion over 30-90 min q3wk
Docetaxel: 75 mg/m² IV infusion initially; may increase to 100 mg/m² IV infusion q3wk if initial dose is well tolerated
Neoadjuvant Treatment of Breast Cancer
Indicated in combination with trastuzumab and docetaxel 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
Initial dose: 840 mg IV infusion over 60 min, THEN 420 mg IV infusion over 30-60 min q3wk
Trastuzumab: 8 mg/kg IV infusion over 90 min initially, then 6 mg/kg IV infusion over 30-90 min q3wk
Docetaxel: 75 mg/m² IV infusion initially; may increase to 100 mg/m² IV infusion q3wk if initial dose is well tolerated
Neoadjuvant dosage regimens
- Administered q3wk for 3 to 6 cycles as part of 1 of the following treatment regimens for early breast cancer:
- - 4 preoperative cycles of pertuzumab in combination with trastuzumab and docetaxel followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC)
- -3 preoperative cycles of FEC alone followed by 3 preoperative cycles of pertuzumab in combination with docetaxel and trastuzumab
- -6 preoperative cycles of pertuzumab in combination with docetaxel, carboplatin, and trastuzumab (TCH) (escalation of docetaxel above 75 mg/m2 is not recommended)
- Following surgery, patients should continue to receive trastuzumab to complete 1 year of treatment
Dosage modifications
Withhold or discontinue pertuzumab if trastuzumab is withheld or discontinued; may continue therapy with trastuzumab if docetaxel has been discontinued
Pertuzumab dose reductions are not recommended
Delayed or missed dose
- Time between 2 doses <6 weeks: Administer 420 mg
- Time between 2 doses >6 weeks: Administer initial dose of 840 mg, then subsequent doses of 420 q3wk
Hypersensitivity
- Interrupt or decrease infusion rate if infusion-related reaction occurs
- Discontinue immediately if severe hypersensitivity reaction occurs
Left ventricular ejection fraction (LVEF)
- Withhold pertuzumab and trastuzumab for at least 3 weeks if:
- -LVEF drops to <40% or,
- -40-45% with >10% absolute decrease below pretreatment values
- -Resume therapy if LVEF >45% or 40-45% with <10% absolute decrease below baseline
- -If LVEF has worsened or not improved after 3 weeks, discontinue pertuzumab and trastuzumab, unless the benefits for the individual patient are deemed to outweigh the risks
Dosing Considerations
Safety as part of a doxorubicin-containing regimen has not been established
Neoadjuvant treatment of 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
- Safety of administration for >6 cycles for early breast cancer has not been established
Gastric Cancer (Orphan)
Orphan designation for treatment of gastric cancer
Orphan sponsor
- Genentech, Inc.; 1 DNA Way; South San Francisco, CA 94080-4990
Administration
For IV infusion only; do not administer as IV push or bolus
Monitor for infusion related adverse effects (eg, hypersensitivity, pyrexia, chills, headache, fatigue, asthenia, vomiting) for 60 minutes following first infusion, and for 30 minutes following subsequent infusions
Pertuzumab, trastuzumab, and docetaxel should be administered sequentially
Pertuzumab and trastuzumab can be given in any order
Pediatric dosage forms and strengths
Safety and efficacy not established
Perjeta (pertuzumab) adverse (side) effects
>10%
Diarrhea (66.8%)
Alopecia (60.9%)
Neutropenia (52.8%)
Nausea (42.3%)
Fatigue (37.6%)
Rash (33.7%)
Peripheral neuropathy (32.4%)
Decreased appetite (29.2%)
Mucosal inflammation (27.8%)
Asthenia (26%)
Vomiting (24.1%)
Anemia (23.1%)
Peripheral edema (23.1%)
Nail disorder (22.9%)
Myalgia (22.9%)
Headache (20.9%)
Stomatitis (18.9%)
Pyrexia (18.7%)
Dysgeusia (18.4%)
Leukopenia (18.2%)
Upper respiratory tract infection (16.7%)
Arthralgia (15.5%)
Constipation (15%)
Pruritus (14%)
Dyspnea (14%)
Increased lacrimation (14%)
Febrile neutropenia (13.8%)
Insomnia (13.3%)
Dizziness (12.5%)
Nasopharyngitis (11.8%)
Dry skin (10.6%)
1-10%
Hypersensitivity (10%)
Paronychia (7.1%)
Pleural effusion (5.2%)
Left ventricular dysfunction (4.4%)
Congestive heart failure (1%)
Postmarketing Reports
Thrombocytopenia
Infusion reactions
Note: Adverse reaction were reported less frequently after discontinuing docetaxel; all adverse reactions in the pertuzumab/trastuzumab treatment group occurred in <10% of patients with the exception of diarrhea (19.1%), UTI (12.8%), rash (11.75%), headache (11.4%), and fatigue (11.1%)
Warnings
Black box warnings
Exposure in pregnant women may result in embryo-fetal death and birth defects
Animal studies have observed oligohydramnios, delayed renal development, and death
Advise patients of these risks and the need for effective contraception
Therapy can result in subclinical and clinical cardiac failure; evaluate left ventricular function in all patients prior to and during therapy; discontinue therapy if significant decrease in left ventricular function confirmed
Contraindications
Hypersensitivity
Cautions
Verify pregnancy status of females of reproductive potential prior to the initiation of therapy; advise pregnant women and females of reproductive potential that therapy during pregnancy or within 7 months prior to conception can result in fetal harm; if pertuzumab administered during pregnancy or if patient becomes pregnant while receiving pertuzumab or within 7 months following last dose of pertuzumab in combination with trastuzumab, immediately report exposure to Genentech Adverse Event Line at 1-888-835-2555; encourage women who may be exposed during pregnancy or within 7 months for pertuzumab in combination with trastuzumab prior to conception, to enroll in the MOTHER Pregnancy Registry by contacting 1-800-690-6720; if pregnancy occurs during treatment, monitor for oligohydramnios
Infusion related adverse effects reported; monitor during and after infusion (see Administration)
Decreased left ventricular ejection fraction (LVEF) reported with HER2 blockers; assess LVEF at baseline and q3 months (also see Dosage modifications)
Severe hypersensitivity, including anaphylaxis observed
HER2 testing: Detection of HER2 protein overexpression required for selection of patients appropriate for pertuzumab therapy
Pregnancy and lactation
Pregnancy category: D; based on animal studies, may cause fetal harm including oligohydramnios, delayed fetal kidney development, and embryofetal death (see Black box warnings)
Lactation: Unknown whether distributed in breast milk; because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue breast feeding or discontinue the drug, taking into account the importance of the drug to the mother
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Perjeta (pertuzumab)
Mechanism of action
Monoclonal antibody that binds to the extracellular dimerization domain of the human epidermal growth factor receptor 2 protein (HER2); mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells that overexpress HER2
Elimination
Half-life: 18 days
Total body clearance: 0.24 L/day
Administration
IV Compatibilities
0.9% NaCL
IV Preparation
Withdraw appropriate volume for desired dose from vial(s)
Dilute measured dose into 0.9% NaCl 250 ml infusion bag (dilute with 0.9% NaCl only, do not use dextrose solution)
Do not shake; mix diluted solution by gentle inversion
Administer immediately once prepared or store refrigerated (see Storage)
IV Administration
Administer initial dose as IV infusion over 60 minutes; subsequent doses may be administered over 30-60 minutes
Interrupt or decrease infusion rate if infusion-associated reaction occurs
Administer by IV infusion only; do not give IV push
Storage
Unopened vials are stable until date indicated on package when stored refrigerated 2-8°C (36-46°F) in carton and protected from light
Diluted solution: May be stored refrigerated at 2-8°C (36-46°F) for up to 24 hr
