Drug Detail:Perjeta (Pertuzumab [ per-too-zoo-mab ])
Generic Name: PERTUZUMAB 30mg in 1mL
Dosage Form: injection, solution, concentrate
Drug Class: HER2 inhibitors
Patient Selection
Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage (1) and Clinical Studies (14)]. 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. Information on the FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics.
Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results.
Recommended Doses and Schedules
The initial dose of PERJETA is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes.
When administered with PERJETA, the recommended initial dose of trastuzumab is 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes.
When administered with PERJETA, the recommended initial dose of trastuzumab hyaluronidase-oysk is 600 mg/10,000 units (600 mg trastuzumab and 10,000 units hyaluronidase) administered subcutaneously over approximately 2 to 5 minutes once every three weeks irrespective of the patient's body weight.
PERJETA, trastuzumab or trastuzumab hyaluronidase-oysk, and taxane should be administered sequentially. PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk can be given in any order. Taxane should be administered after PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk. An observation period of 30 to 60 minutes is recommended after each PERJETA infusion and before commencement of any subsequent administration of trastuzumab or trastuzumab hyaluronidase-oysk, or taxane [see Warnings and Precautions (5.3)].
In patients receiving an anthracycline-based regimen, PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk should be administered following completion of the anthracycline.
Metastatic Breast Cancer (MBC)
When administered with PERJETA, the recommended initial dose of docetaxel is 75 mg/m2 administered as an intravenous infusion. The dose may be escalated to 100 mg/m2 administered every 3 weeks if the initial dose is well tolerated.
Neoadjuvant Treatment of Breast Cancer
PERJETA should be administered every 3 weeks for 3 to 6 cycles as part of one of the following treatment regimens for early breast cancer [see Clinical Studies (14.2)]:
- Four preoperative cycles of PERJETA in combination with trastuzumab or trastuzumab hyaluronidase-oysk and docetaxel followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) as given in NeoSphere
- Three or four preoperative cycles of FEC alone followed by 3 or 4 preoperative cycles of PERJETA in combination with docetaxel and trastuzumab or trastuzumab hyaluronidase-oysk as given in TRYPHAENA and BERENICE, respectively
- Six preoperative cycles of PERJETA in combination with docetaxel, carboplatin, and trastuzumab (TCH) or trastuzumab hyaluronidase-oysk (escalation of docetaxel above 75 mg/m2 is not recommended) as given in TRYPHAENA
- Four preoperative cycles of dose-dense doxorubicin and cyclophosphamide (ddAC) alone followed by 4 preoperative cycles of PERJETA in combination with paclitaxel and trastuzumab or trastuzumab hyaluronidase-oysk as given in BERENICE
Following surgery, patients should continue to receive PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk to complete 1 year of treatment (up to 18 cycles).
Adjuvant Treatment of Breast Cancer
PERJETA should be administered in combination with trastuzumab or trastuzumab hyaluronidase-oysk every 3 weeks for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first, as part of a complete regimen for early breast cancer, including standard anthracycline- and/or taxane-based chemotherapy as given in APHINITY. PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk should start on Day 1 of the first taxane-containing cycle [see Clinical Studies (14.3)].
Dose Modification
For recommendations on delayed or missed doses, please refer to Table 1.
| Time between two sequential doses | PERJETA | Trastuzumab (intravenous) |
Trastuzumab hyaluronidase-oysk |
|---|---|---|---|
| < 6 weeks | Administer PERJETA 420 mg intravenously as soon as possible. Do not wait until the next planned dose. | Administer trastuzumab 6 mg/kg intravenously as soon as possible. Do not wait until the next planned dose. | Administer trastuzumab hyaluronidase-oysk 600 mg/10,000 units subcutaneously as soon as possible. Do not wait until the next planned dose. |
| ≥ 6 weeks | Readminister PERJETA loading dose of 840 mg intravenously as a 60 minute infusion, followed by a maintenance dose of 420 mg administered intravenously over a period of 30 to 60 minutes every 3 weeks thereafter. | Readminister trastuzumab loading dose of 8 mg/kg intravenously over approximately 90 minutes, followed by a maintenance dose of 6 mg/kg administered intravenously over a period of 30 or 90 minutes every 3 weeks thereafter. |
PERJETA should be discontinued if trastuzumab or trastuzumab hyaluronidase-oysk treatment is discontinued.
Dose reductions are not recommended for PERJETA.
For chemotherapy dose modifications, see relevant prescribing information.
Left Ventricular Ejection Fraction (LVEF):
Assess left ventricular ejection fraction (LVEF) prior to initiation of PERJETA and at regular intervals during treatment as indicated in Table 2. The recommendations on dose modifications in the event of LVEF dysfunction are also indicated in Table 2 [see Warnings and Precautions (5.1)].
| Pre-treatment LVEF: | Monitor LVEF every: | Withhold PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk for at least 3 weeks for an LVEF decrease to: | Resume PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk after 3 weeks if LVEF has recovered to: | |||
|---|---|---|---|---|---|---|
|
||||||
| Metastatic Breast Cancer | ≥ 50% | ~12 weeks | Either | Either | ||
| <40% | 40%-45% with a fall of ≥10%-points below pre-treatment value | >45% | 40%-45% with a fall of <10%-points below pre-treatment value | |||
| Early Breast Cancer | ≥ 55%* | ~12 weeks (once during neoadjuvant therapy) | <50% with a fall of ≥10%-points below pre-treatment value | Either | ||
| ≥50% | <10% points below pre-treatment value | |||||
Preparation for Administration
Administer as an intravenous infusion only. Do not administer as an intravenous push or bolus. Do not mix PERJETA with other drugs.
Preparation
Prepare the solution for infusion, using aseptic technique, as follows:
- Parenteral drug products should be inspected visually for particulates and discoloration prior to administration.
- Withdraw the appropriate volume of PERJETA solution from the vial(s) using a sterile needle and syringe.
- Dilute into a 250 mL 0.9% sodium chloride PVC or non-PVC polyolefin infusion bag.
- Mix diluted solution by gentle inversion. Do not shake.
- Administer immediately once prepared.
- If the diluted infusion solution is not used immediately, it can be stored at 2°C to 8°C for up to 24 hours.
- Dilute with 0.9% Sodium Chloride injection only. Do not use dextrose (5%) solution.
