他泽司他对于上皮样肉瘤的用药效果？

Tazerestat is a new drug for the treatment of sarcoma developed and marketed by Epizyme. The drug was approved by the U.S. Food and Drug Administration on January 23, 2020. It is used to treat metastatic/locally advanced epithelioid sarcoma that is not suitable for complete resection in patients aged 16 years and above. The clinical effect is significant, and patients can use the drug correctly under the guidance of a doctor.

epithelioid sarcoma

Epithelioid sarcoma is a rare type of soft tissue sarcoma, accounting for less than 1% of all soft tissue sarcomas. Epithelioid sarcomas mostly originate in the subcutaneous soft tissues of the extremities. Before cancer cells metastasize, surgical resection is the main treatment method. Chemotherapy and radiotherapy can also be used. However, epithelioid sarcoma is very prone to metastasis. Even after active treatment, epithelioid sarcoma is still likely to metastasize locally or between regions. About 50% of patients have already metastasized when they are diagnosed.

On January 23, 2020, the U.S. FDA approved Epizyme Inc.'s new drug tazerestat through the accelerated approval process (Accelerated Approval) for the treatment of metastatic or locally advanced epithelioid sarcoma (Epithelioid sarcoma) in adults and adolescent patients aged 16 years and above. It is suitable for patients who cannot completely remove the tumor through surgery. Tazerestat is the first drug approved by the FDA to treat epithelioid sarcoma.

The use of tazetostat in epithelioid sarcoma

Background: Epithelioid sarcoma is a rare, aggressive subtype of soft tissue sarcoma. In one study, the clinical activity and safety of tazerestat was reported in patients with epithelioid sarcoma.

Methods: In this open phase 2 basket study, patients were divided into 7 groups, each with a different INI1-negative solid tumor or synovial sarcoma. Patients received tazerestat 800 mg in consecutive 28-day cycles until disease progression and unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate according to Response Evaluation Criteria in Solid Tumors (version 1.1). Secondary endpoints were duration of response, disease control rate at 32 weeks, progression-free survival, overall survival, and pharmacokinetic and pharmacodynamic analyzes (primary results reported elsewhere).

Results: Between December 22, 2015, and July 7, 2017, 62 patients with epithelioid sarcoma were enrolled in the study and deemed eligible for inclusion in the cohort. Nine of 62 patients (15% [95% CI 7-26]) had an objective response at data cutoff (September 17, 2018). At a median follow-up of 138 months (IQR 78-190), the median duration of response had not been reached (95% CI 92-not estimable). Sixteen (26% [95% CI 16-39]) patients had disease control at 32 weeks. The median time to response was 39 months. Median progression-free survival was 5.5 months (95% CI 3.4-5.9) and median overall survival was 190 months (110-not estimable).

Conclusion:

Tazerestat is well tolerated and clinically active in patients with advanced epithelioid sarcoma characterized by INI1/SMARCB1 loss. Tazetostat has the potential to improve outcomes in patients with advanced epithelioid sarcoma.

Effect of tazetostat on relapsed or refractory follicular lymphoma

Background: Approximately 20% of patients with follicular lymphoma have activating mutations in the epigenetic regulator EZH2. The activity and safety of tazerestat was studied in patients with follicular lymphoma.

Methods: The study was conducted at 38 clinical centers in France, the United Kingdom, Australia, Canada, Poland, Italy, Ukraine, Germany, and the United States. Inclusion criteria were adults (18 years of age) with pathologically confirmed follicular lymphoma (grades 1, 2, 3 a, 3 b), relapsed or refractory to two or more systemic therapies, having an Eastern Cooperative Oncology Group performance status of 0-2, and having sufficient tumor tissue for central testing of EZH2 mutation status.

The patient received tazerestat 800 mg twice daily for 28 days as a cycle. The primary endpoint was objective response rate based on the 2007 International Working Group on Non-Hodgkin Lymphoma criteria.

Results: Of 99 patients, 54 (in the EZH2WT cohort) participated in the study. At the data cutoff point of the analysis (August 9, 2019), the median follow-up time was 22±0 months for the EZH2mut cohort and 35±9 months for the EZH2WT cohort. The objective response rate was 69% (95% confidence interval, 53-82; 31 of 45 patients) and 35% (23-49; 19 of 54 patients). Median duration of response was 10±9 months (95% CI 7±2-not estimable [NE]) in the EZH2mut cohort and 13±0 months (5±6-NE) ​​in the EZH2WT cohort; median progression-free survival was 138 months (107-220) and 111 months (37-146), respectively.

Conclusion: Tazerestat alone has good clinical efficacy and good tolerability in relapsed and refractory follicular lymphoma. Tazetostat is a new treatment for patients with follicular lymphoma.

Summary

Tazerestat has a significant effect on epithelioid sarcoma. In addition, it also has a significant effect on the treatment of relapsed or refractory follicular lymphoma. If the patient has the above drug indications, it is recommended to consult a doctor in advance and use medication under the guidance of the doctor.

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