Pertuzumab

Pertuzumab instructions
Common name: Pertuzumab
Trade name: Perjeta
All names: Pertuzumab, Pertuzumab, Pertuzumab, Perjeta

Indications:
This product is suitable for use in combination with trastuzumab and chemotherapy as adjuvant therapy for patients with HER2-positive early breast cancer with a high risk of recurrence.

Usage and Dosage:
The initial dose is 840 mg as an intravenous infusion over 60 minutes. Thereafter, 420 mg was administered as an intravenous infusion over 30 to 60 minutes every 3 weeks.

Adverse Reactions:
The most common adverse reactions (>30%) with pertuzumab in combination with trastuzumab and docetaxel are diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.

Contraindications:
Pertuzumab is contraindicated in patients with known hypersensitivity to pertuzumab or any of its excipients.

Precautions:
(1) Embryo-fetal toxicity: Fetal harm may occur if administered to pregnant women.
(2) Left ventricular dysfunction: monitor LVEF and withdraw administration when appropriate.
(3) Infusion-related reactions, hypersensitivity reactions/anaphylaxis: Monitor for signs and symptoms. If a major infusion-related reaction occurs, slowing down or interrupting the infusion should result in appropriate medical treatment.
(4) HER2 Testing: Performed by a proven proficient laboratory using an FDA-approved test.

Storage:
Protect from light and store in refrigerator at 2°C to 8°C (36°F to 46°F)

Mechanism of Action:
Palbociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. Cyclin D1 and CDK4/6 are downstream of signaling pathways leading to cell proliferation. In vitro, palbociclib reduces cell proliferation in estrogen receptor (ER)-positive breast cancer cell lines by blocking cell progression from G1 to S phase of the cell cycle. Combined treatment of breast cancer cell lines with palbociclib and antiestrogen results in reduced retinoblastoma protein (Rb) phosphorylation leading to reduced E2F expression and signaling and prevents increased growth compared to treatment with each drug alone. Combined treatment of ER-positive breast cancer cell lines with palbociclib and antiestrogen in vitro resulted in increased cellular senescence that persisted up to 6 days after drug removal. In vivo studies using a patient-derived ER-positive breast cancer xenograft animal model showed that the palbociclib and letrozole combination increased Rb phosphorylation, downstream signaling, and inhibition of tumor growth compared with each drug alone.

Efficacy and Safety:
The safety of pertuzumab has been evaluated in more than 6,000 cancer patients in clinical trials, including the pivotal clinical trials CLEOPATRA (n= 808), NEOSPHERE (n= 417), TRYPHAENA (n= 225) and APHINITY (n= 4804), patients mainly received pertuzumab combined with other anti-tumor drugs. The most common adverse drug reactions and incidence rates observed vary between studies and are related to pertuzumab monotherapy or combined with other anti-tumor drugs, but the overall study results show that the safety profile of pertuzumab is basically consistent.