阿培利司 用于经基于内分泌的治疗方案治疗后疾病进展的携带PIK3CA突变的激素受体阳性、人表皮生长因子受体-2阴性(HR+/HER2-)的晚期或转移性乳腺癌患者。

Apellis instruction manual

Product Name: LuciAlpe

Manufacturer: Lucius Pharmaceuticals

Chinese name: Apellis

English name: Alpelisib

Drug approval number: 03 L 1076/24

 

 

【Summary】

Alpelisib is a phosphatidylinositol 3-kinase (PI3K) inhibitor that can inhibit PI3Kα (PIK3CA) activity and induce increased transcription of estrogen receptors in breast cancer cells. It has synergistic anti-tumor activity when used in combination with fulvestrant.

 

【Indications】

For the treatment of patients with hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-) advanced or metastatic breast cancer with PIK3CA mutation whose disease has progressed after endocrine-based therapy.

 

【Specification】  

150mg/tablet, 28 tablets/bottle.

 

【Storage】

Store at 20°C to 25°C (68°C to 77°F); short-distance transport is permitted at a temperature range of 15 to 30°C (59–86°F).

 

【 Usage and Dosage

1. Recommended dose: 300 mg (two 150 mg tablets), once a day, taken orally with food.

2. Swallow the tablet whole. Do not chew, break or crush the tablet.

3. For adverse reactions, please consider dose interruption, dose reduction or discontinuation

 

【 Adverse Reactions 】

1.>10%:

1. Cardiovascular: peripheral edema (15%)

2. Central nervous system: fatigue (42%), headache (18%)

3. Dermatology: rash (52%), hair loss (20%), itching (18%), xerosis (18%)

4. Endocrine and metabolism: hyperglycemia (65%), increased γ-glutamyl transferase (52%), decreased serum calcium (27%), weight loss (27%), decreased blood sugar (26%), decreased serum albumin (14%), decreased serum potassium (14%), decreased serum magnesium (11%)

5. Gastrointestinal: diarrhea (58%), nausea (45%), increased serum lipase (42%), decreased appetite (36%), stomatitis (19% to 30%; Grade 3/4: 2% to 3%), vomiting (27%), loss of appetite (18%), abdominal pain (17%), dry mucosa (12%), dyspepsia (11%)

6. Hematology and Oncology: Lymphocytopenia (52%; Grade 3/4: 8%), prolonged partial thromboplastin time (21%; Grade 3/4: <1%), decreased platelet count (14%; Grade 3/4: 1%)

7. Liver: Elevated serum alanine aminotransferase (44%)

8. Kidney: increased serum creatinine (67%)

9. Others: Fever (14%)

2. 1% - 10%:

1. Dermatology: erythema multiforme (1%)

2. Gastrointestinal tract: severe diarrhea (3%)

3. Urogenital system: urinary tract infection (10%)

4. Hematology and Oncology: Anemia (2%)

5. Neuromuscular and skeletal: Osteonecrosis of the jaw (4%)

6. Kidney: Acute renal failure (3%)

7. Respiratory tract: pneumonia (2%)

3. Undefined frequency:

1. Dermatology: chapped skin

2. Gastrointestinal tract: senile dry mouth

3. Urogenital system: vaginal dryness

4. Neuromuscular and skeletal: Weakness

4. <1%:

Postmarketing and case reports:

1. Anaphylactic shock, allergic reaction, interstitial pneumonia, interstitial lung disease

2. Ketoacidosis, severe skin disease reactions, severe allergic reactions

3. Stevens-Johnson syndrome, urinary tract infection and sepsis 

 

【 Notes 】

1. Severe allergic reaction: Permanently discontinue Alpelisib and start appropriate treatment promptly.

2. Severe skin reactions: Cases of severe skin reactions have been reported, including Stevens-Johnson syndrome (SJS) and erythema multiforme (EM). Do not treat patients with a history of Smith, EM, or toxic epidermal necrolysis (TEN). If symptoms of severe skin reactions are present, interrupt Alpelisib until the cause of the reaction is determined. Consider consulting a dermatologist. If SJS, EM, or TEN is confirmed, permanently stop Alpelisib.

3. Hyperglycemia: Severe hyperglycemia, including ketoacidosis, has been reported. The safety of Alpelisib in patients with type 1 or uncontrolled type 2 diabetes has not been established. Before starting treatment with Alpelisib, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. After starting treatment, monitor during. Initiate or optimize antihyperglycemic medications as clinically indicated. If severe hyperglycemia occurs, interrupt, reduce the dose, or stop Alpelisib.

4. Pneumonitis: Severe pneumonitis and interstitial lung disease have been reported. Monitor clinical symptoms or radiological changes. If severe pneumonitis occurs, interrupt or stop Alpelisib.

5. Diarrhea: Severe cases of diarrhea, including dehydration and acute kidney injury, have been reported. Most patients experience diarrhea (≤Grade 2) during treatment with Alpelisib. Patients are advised to start anti-diarrhea treatment, increase oral fluids, and notify medical staff if diarrhea occurs. If diarrhoea occurs, interrupt, reduce the dose, or stop Alpelisib.

6. Embryo-fetal toxicity: Alpelisib can cause fetal harm. Inform patients of the potential risk to the fetus and use effective contraception.

 

【Efficacy and safety】

In patients with PIK3CA mutations, the experimental group (apellisir + fulvestrant) was compared with the control group (placebo + fulvestrant): Median progression-free survival: 11.0 vs. 5.7 months, one-year progression-free survival rate: 46.3% vs. 32.9%, progression + death risk ratio: 0.65, complete + partial remission rate: 26.6% vs. 12.8%;

In patients without PIK3CA mutations, the experimental group (apellisir + fulvestrant) was compared with the control group (placebo + fulvestrant): median progression-free survival: 7.4 vs. 5.6 months, one-year progression-free survival rate: 28.4% vs. 22.2%, and the risk ratio of progression + death: 0.85.

The results of the trial showed that among patients with hormone receptor-positive HER2-negative advanced breast cancer who had failed endocrine therapy, patients with PIK3CA mutations could significantly prolong progression-free survival by receiving apellis plus fulvestrant treatment.

The incidence of adverse events in clinical trials: the incidence of grade 3-4 hyperglycemia: 36.6% vs. 0.7%; the incidence of grade 3-4 rash: 9.9% vs. 0.3%; the incidence of grade 3 diarrhea: 6.7% vs. 0.3%; the incidence of discontinuation due to adverse events: 25.0% vs. 4.2%.

 

【Taboo】

Severe allergic reaction to alpelisib or any of its ingredients.