Pertuzumab: Uses,Dosage,Side Effects

Generic Name

Pertuzumab
Therapeutic Class: Monoclonal Antibody (Targeted Cancer Therapy)

Indications:
Pertuzumab is a HER2/neu receptor antagonist indicated for:

Use in combination with trastuzumab and docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Use in combination with trastuzumab and chemotherapy 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.
• Adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence

Presentation:
Pertuzumab 420: Each vial contains Pertuzumab INN 420 mg in 14 ml solution for IV infusion

Description:
Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular
dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2).
Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal
growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of
HER2 with other HER family members, including EGFR, HER3, and HER4. As a result, Pertuzumab
inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated
protein (MAP) kinase, and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways
can result in cell growth arrest and apoptosis, respectively. In addition, Pertuzumab mediates
antibody-dependent cell-mediated cytotoxicity

Dosage & Administration:
For intravenous infusion only. Do not administer as an intravenous push or bolus.

HER2 testing: Perform using FDA-approved tests by laboratories with demonstrated proficiency.
The initial Pertuzumab dose is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by 420 mg administered as a 30 to 60-minute intravenous infusion.

MBC: Administer Pertuzumab, trastuzumab, and docetaxel by intravenous infusion every 3 weeks.
Neoadjuvant: Administer Pertuzumab, trastuzumab, and chemotherapy by intravenous infusion preoperatively every 3 weeks for 3 to 6 cycles.
Adjuvant: Administer Pertuzumab, trastuzumab, and chemotherapy by intravenous infusion postoperatively every 3 weeks for a total of 1 year (up to 18 cycles).

Side Effects:
Metastatic Breast Cancer:

• The most common adverse reactions (> 30%) with Pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.

Neoadjuvant Treatment of Breast Cancer:

• The most common adverse reactions (> 30%) with Pertuzumab in combination with trastuzumab and docetaxel were alopecia, diarrhea, nausea, and neutropenia.
• The most common adverse reactions (>30%) with Pertuzumab 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 adverse reactions (>30%) with Pertuzumab in combination with docetaxel, carboplatin, and trastuzumab (TCH) were fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, and anemia.
• The most common adverse reactions (>30%) with Pertuzumab in combination with trastuzumab and paclitaxel when given for 4 cycles following 4 cycles of ddAC were nausea, diarrhea, alopecia, fatigue, constipation, and headache.
• The most common adverse reactions (>30%) with Pertuzumab in combination with trastuzumab and docetaxel when given for 4 cycles following 4 cycles of FEC were diarrhea, nausea, alopecia, asthenia, constipation, fatigue, mucosal inflammation, vomiting, myalgia, and anemia. Adjuvant Treatment of 

Breast Cancer:

• The most common adverse reactions (>30%) with Pertuzumab in combination with trastuzumab and chemotherapy were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting.

Precautions:
Left Ventricular Dysfunction: LVEF should be monitored and dosing should be withheld as appropriate
Embryo-fetal toxicity: Fetal harm can occur when administered to a pregnant woman
Infusion-Related Reactions: Should be monitored for signs and symptoms. If a significant
the infusion-associated reaction occurs, the infusion should be slowed or interrupted, and appropriate
medical therapies should be administered
Hypersensitivity Reactions/Anaphylaxis: Should be monitored for signs and symptoms. If a severe
hypersensitivity reaction/anaphylaxis occurs, the infusion should be discontinued immediately and
appropriate medical therapies should be administered

Pregnancy & Lactation:
Pregnancy Category D
There are no adequate and well-controlled studies of Pertuzumab in pregnant women. If Pertuzumab
is administered during pregnancy or if a patient becomes pregnant while receiving Pertuzumab or
within 7 months following the last dose of Pertuzumab in combination with Trastuzumab, the patient
should be apprised of the potential hazard to the fetus
Lactation
It is not known whether Pertuzumab is excreted in human milk, but human IgG is excreted in human
milk. Because many drugs are secreted in human milk and because of the potential for serious
adverse actions in nursing infants from Pertuzumab a decision should be made whether to discontinue
nursing, or discontinue the drug, taking into account the elimination half-life of Pertuzumab and the
importance of the drug to the mother
Pediatric Use
The safety and effectiveness of Pertuzumab have not been established in pediatric patients.

Interaction:
Patients who receive anthracycline after stopping Pertuzumab may be at increased risk of cardiac
dysfunction because of Pertuzumab’s long washout period. If possible, physicians should avoid
anthracycline-based therapy for up to 7 months after stopping Pertuzumab. If anthracyclines are
used, the patient’s cardiac function should be monitored carefully.

Storage:
Store vials in a refrigerator at 2°C to 8°C until time of use. Keep the vial in the outer carton in order to protect it from light.