Instructions for Pertuzumab

1. Generic name: Pertuzumab

Product name:Perjeta

All names: Perget, Pertuzumab, Pertuzumab

2. Indications:

1. Metastatic breast cancer (MBC):

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

2. Early breast cancer (EBC):

Pertuzumab is suitable for use in combination with trastuzumab and chemotherapy; as part of a complete treatment plan for early breast cancerNeoadjuvant therapy for patients with HER2-positive, locally advanced, inflammatory or early breast cancer (larger than 2cm in diameter or positive lymph nodes), and adjuvant therapy for patients with HER2-positive early breast cancer with a high risk of recurrence.

3. Usage and dosage:

1. Recommended dosage:

The initial dose of pertuzumab is 840 mg as an intravenous infusion over 60 minutes, followed by 420 mg as an intravenous infusion over 30 to 60 minutes every 3 weeks. When administered with pertuzumab, the recommended initial dose of trastuzumab is 8 mg/kg as an intravenous infusion over 90 minutes, followed by 6 mg/kg as an intravenous infusion over 30 to 90 minutes every 3 weeks. The recommended initial dose of trastuzumab hyaluronidase-oysk is 600 mg/10,000 units (600 mg trastuzumab and 10,000 units hyaluronidase) administered subcutaneously every three weeks for approximately 2-5 minutes, regardless of patient weight.

(1) Metastatic breast cancer (MBC): When administered withpertuzumab , the recommended initial dose of docetaxel (docetaxel) is 75 mg/m2 administered by intravenous infusion. If the initial dose is well tolerated, the dose may be increased to 100 mg/m2 every 3 weeks.

(2) Neoadjuvant treatment of breast cancer:Pertuzumab will be administered every 3 weeks for 3-6 cycles as part of one of the early breast cancer treatment regimens, and patients should continue to receive it after surgeryPertuzumaband trastuzumab or trastuzumab hyaluronidase-oysk treatment to complete 1 year of treatment (up to 18 cycles).

(3) Adjuvant treatment of breast cancer:Pertuzumab should be used in combination with trastuzumab or trastuzumab hyaluronidase-oysk, once every 3 weeks for a total of 1 year< span> (up to 18 cycles), or until disease recurrence or uncontrollable toxicity, as part of a complete regimen for early breast cancer, including standard anthracycline and/or taxane chemotherapy given in the Appendix. Pertuzumaband trastuzumab or trastuzumab hyaluronidase-oysk should be initiated on Day 1 of the first taxane-containing cycle.

2. Dosage adjustment:

Pertuzumab dose reduction is not recommended and Pertuzumab should be discontinued if trastuzumab or trastuzumab hyaluronidase-oysk treatment is discontinued.

4. Adverse reactions:

In clinical trials of a three-drug combination for metastatic breast cancer, more than half of people taking the drug experienced side effects including diarrhea, alopecia, and neutropenia; more than10% experienced neutropenia and leukopenia accompanied by fever. The most common adverse reactions reported by some patients after discontinuing docetaxel are diarrhea, upper respiratory tract infection, rash, headache, fatigue, nasal and throat swelling (usually caused by colds), weakness, itching, joint pain, nausea, limb pain, and back pain. In clinical trials of neoadjuvant use of this combination in breast cancer, more than 50% of people experienced alopecia and neutropenia.

After pertuzumab is marketed, patients may develop tumor lysis syndrome (TLS). Patients with significant tumor burden (eg, massive metastases) may be at higher risk. Patients may develop hyperuricemia, hyperphosphatemia, and acute renal failure, which may represent TLS.

5. Storage:

Pertuzumab is an injectable, containing preservative-free solution. Until use, store vials in Store vials in the outer carton away from light in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Don't shake.

6. Taboo:

Contraindicated in patients with known hypersensitivity to pertuzumab or any of its excipients.

7. Mechanism of action:

Pertuzumab targets the extracellular dimerization domain (subdomain II) of the human epidermal growth factor receptor 2 protein (HER2), thereby blocking the ligand-dependent heterodimerization of HER2 with other HER family members. Pertuzumab therefore inhibits ligand-initiated intracellular signaling through two major signaling pathways, namely mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K). Inhibiting these signaling pathways can lead to cell growth arrest and apoptosis, respectively. In addition, Pertuzumab mediates antibody-dependent cell-mediated cytotoxicity (ADCC). While pertuzumab alone inhibits the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab enhanced antitumor activity in a xenograft model of HER2 overexpression.

8. Special groups:

1. Females: Based on the mechanism of action and animal data, pertuzumab administration during pregnancy can cause embryo -fetal damage. It is recommended that females of reproductive potential use effective contraception during treatment and for 7 months after the last dose of pertuzumab in combination with trastuzumab.

Pertuzumab is a strictly controlled drug. The original drug has been marketed in China and has entered the ranks of medical insurance, but it is only reimbursed for patients who meet the indications. The price of each box may be more than more than 5,000 yuan, and the price of the Hong Kong version may be more than 20,000 yuan (the price may fluctuate due to exchange rates). The price of each box of the European version of Pertuzumab's original drug marketed overseas may be more than 10,000 yuan, and the price of each box of the Turkish version may be more than 6,000 yuan (the price may fluctuate due to exchange rates). The ingredients of the domestic and foreign original drugs are basically the same, and there are currently no generic versions of Pertuzumab on the market.