Instructions for Alpelisib-Piqray

1. Common name: Apelvis

Product name:PIQRAY

Full names: Alpelisib, Alpelisib, Alpelisib

2. Indications:

Alpelisib may be combined with fulvestrant for the treatment of postmenopausal women and men with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test during or after an endocrine-based regimen.

3. Usage and dosage:

1. Before treatment: Based on the presence of one or more PIK3CA mutations in tumor tissue or plasma specimens, doctors will select patients with HR-positive, HER2-negative advanced or metastatic breast cancer to use Apelvis to treat. If no mutations are detected in the plasma specimen, tumor tissue is tested.

2. Recommended dose: The recommended dose of Apelvis is 300 mg once daily (Two tablets 150 mg film-coated tablets), taken with food, and treatment continues until the disease worsens or unacceptable toxicity occurs. The recommended dose of fulvestrant when administered with apelvis is 500 mg on days 1, 15 and 29 and monthly thereafter, subject to adjustment based on its prescribing information.

3. Dosage adjustment: If the patient experiences adverse reactions during treatment with Apelix, the doctor will adjust the dose according to the severity. The first dose will be reduced to 250 mg once a day (one 200 mg tablet and one 50 mg tablet), and the second dose will be reduced to 200 mg once a day (one 200 mg tablet). If the second dose reduction cannot be tolerated, please permanently discontinue Apellis.

Patients who develop pancreatitis are allowed to reduce the dose of Apelix only once; if severe skin adverse reactions (scarring) are confirmed, Apelix needs to be permanently discontinued. Do not re-administer Apellis to patients with previous scarring during Apelis treatment.

4. Adverse reactions:

In Alpelisib (Alpelisib) - PiqrayIn clinical studies, the most common adverse reactions include diarrhea, rash, nausea, fatigue, decreased appetite, stomatitis, vomiting, weight loss, and hair loss; laboratory abnormalities are increased glucose, increased creatinine, decreased lymphocyte count, increased gamma-glutamyl transferase (GGT), increased alanine aminotransferase (ALT), decreased hemoglobin, increased lipase, decreased calcium, decreased glucose, and prolonged activated partial thromboplastin time (aPTT). ApelixColitis, hyperglycemic hyperosmolar nonketotic syndrome (HHNKS), angioedema, and drug reactions with eosinophilia and systemic symptoms (DRESS) have also occurred since its launch.

5. Storage:

Apellis is stored at a storage temperature of 20°C to 25°C (68°F to 77°F), with an allowed excursion between 15°C and 30°C (59°F to 86°F).

6. Taboo:

Apelix is contraindicated in patients with severe hypersensitivity to it or any of its components.

7. Special groups:

1. Women: According to animal data and mechanism of action, Apelvis can cause harm to the fetus when used by pregnant women and may damage the fertility of female animals. Therefore, it is recommended that women with reproductive potential use effective contraceptive measures during treatment with the drug and within 1 week after the last dose; lactating women are recommended not to breastfeed during treatment with the drug and within 1 week after the last dose.

2. Men: According to the results of animal studies, Apelix may impair the fertility of male animals of reproductive potential. Therefore, male patients with a female partner of reproductive potential are recommended to use condoms and effective contraceptive measures during treatment with Drug Y and within 1 week after the last dose.

8. Mechanism of action:

Apelix is a phosphatidylinositol-3-kinase (PI3K) inhibitor, which mainly has inhibitory activity against PI3Kα. In in vitro and in vivo models, gain-of-function mutations in the gene encoding the PI3K catalytic alpha subunit (PIK3CA) lead to activation of PI3Kα and Akt signaling, cellular transformation, and tumorigenesis. In cancer cell lines, apelvis inhibits phosphorylation of PI3K downstream targets, including Akt, and shows activity in cell lines harboring PIK3CA mutations. In vivo, apelvis inhibits the PI3K/Akt signaling pathway and reduces tumor growth in xenograft models, including cancer models.

In breast cancer cells, inhibition of PI3K by treatment with apelvis induces an increase in estrogen receptor (ER) transcription. In a xenograft model derived from an ER-positive, PIK3CA-mutated cancer breast cancer cell line, the combination of apelvis and fulvestrant showed increased anti-tumor activity compared to treatment alone.