Detailed explanation of the instructions for tazerestat: from indications to medication precautions

Tazemetostat is a new, first-in-class oral small molecule drug that acts as an EZH2 (histone lysine methyltransferase) inhibitor and has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of certain types of cancer. Its unique mechanism of action and clinical application have attracted much attention in the field of tumor treatment.

1. Indications

Tazerestat is mainly suitable for the following patients:

1. Epithelioid Sarcoma (Epithelioid Sarcoma, ES, soft tissue sarcoma ): Applicable to adult and pediatric patients aged 16 and above who have metastatic or locally advanced epithelioid sarcoma and are not suitable for complete resection.

2. Relapsed or refractory follicular lymphoma (Follicular Lymphoma, FL, non-Hodgkin lymphoma):

1) EZH2 gene mutation-positive: Applicable to adult patients whose tumors are confirmed to be EZH2 gene mutation-positive by FDA-approved testing and who have received at least two previous systemic therapies.

2)Patients with no satisfactory alternative treatment options: It is suitable for adult patients with relapsed or refractory follicular lymphoma and no satisfactory alternative treatment options.

2. Usage and dosage

The recommended dose is 800 mg orally twice daily until disease progression or unacceptable toxicity occurs. Tablets should be swallowed whole, with or without food. If you miss a dose or vomit after taking the medicine, you should skip the dose and continue taking the next dose at the regular time without taking a make-up dose.

3. Mechanism of action

Tazerestat selectively inhibits the activity of EZH2 enzyme, preventing it from catalyzing the methylation of histone H3 lysine 27 (H3K27). This methylation often results in the silencing of tumor suppressor genes. By inhibiting EZH2, tazerestat can restore the expression of tumor suppressor genes, thereby inhibiting the growth and proliferation of tumor cells.

4. Clinical research

In a phase 2 clinical trial in patients with epithelioid sarcoma, among 62 patients treated with tazerestat, the overall response rate (ORR) was 15%, with 1.6% achieving a complete response and 13% achieving a partial response. Among patients who responded, 67% had responses that lasted six months or longer.

5. Adverse reactions

Common adverse reactions include:

Patients with epithelioid sarcoma: pain, fatigue, nausea, decreased appetite, vomiting, and constipation.

Patients with follicular lymphoma: Fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.

6. Precautions

1. Secondary malignant tumors: In clinical trials, a small number of patients developed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) after receiving tazerestat. Therefore, long-term monitoring of patients for the development of secondary malignancies is recommended.

2. Embryo-Fetal toxicity: Animal studies have shown that tazerestat may cause harm to the fetus. Women of childbearing potential should use an effective non-hormonal method of contraception during treatment and for 6 months after the last dose. Male patients should use effective contraception during treatment and for at least 3 months after the last dose.

3. Lactating women: It is unclear whether tazerestat is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, it is recommended to avoid breastfeeding during treatment and for one week after the last dose.

4. Hepatic and renal insufficiency: For patients with mild to severe renal insufficiency or end-stage renal disease, no dose adjustment is required. In patients with mild hepatic impairment (total bilirubin> 1 to 1.5 times the upper limit of normal or AST >the upper limit of normal), no dose adjustment is also required. However, it has not been studied in patients with moderate or severe hepatic impairment and should be used with caution.

7. Storage conditions

Drug products should be stored below 30°C (86°F), away from heat and moisture.

Reference materials:https://www.tazverik.com/