他泽司他治疗上皮样肉瘤的疗效？

tazestat

A methyltransferase inhibitor, tazetostat inhibits the proliferation of B-cell lymphoma cell lines in vitro and shows anti-tumor activity in B-cell lymphoma mouse xenograft models with or without EZH2 gain-of-function mutations. The inhibitory effect of tazetostat on proliferation was greater in lymphoma cell lines harboring mutant EZH2.

Tazerestat is indicated for the treatment of adults and pediatric patients 16 years and older with metastatic or locally advanced epithelioid sarcoma who are not candidates for complete resection, and adult patients with relapsed or refractory follicular lymphoma whose tumors test positive for EZH2 mutations.

Tazerestat in the treatment of epithelioid sarcoma

Background: Epithelioid sarcoma is a rare, aggressive subtype of soft tissue sarcoma in which more than 90% of tumors have lost INI1 expression, resulting in oncogenic dependence on the transcriptional repressor EZH2.

Research methods: In an open phase 2 basket study, a total of 62 patients from multiple countries were enrolled and divided into 7 groups, each with different INI1-negative solid tumors or synovial sarcomas.

Results: All 62 patients were included in the modified intention-to-treat analysis, and a total of 15% had an objective response.

At a median follow-up of 13.8 months, the median duration of response had not been reached (95% CI 9 2 - not estimable). Twenty-six percent of patients had disease control at 32 weeks. The median response time was 3.9 months, the median progression-free survival was 5.5 months, and the median overall survival was 19 months. Grade 3 or worse treatment-related adverse events included anemia (6%) and weight loss (3%).

Tazerestat was well tolerated and clinically active in a cohort of patients with advanced epithelioid sarcoma characterized by INI1/SMARCB1 loss. Tazemetostat has the potential to improve outcomes for patients with advanced epithelioid sarcoma.

Usage and dosage

Tazerestat is 800 mg taken twice daily with or without food until disease progression or unacceptable toxicity occurs. Tazerestat must be swallowed whole and the tablets must not be cut, crushed or chewed. If you miss a dose or vomit after taking it, you do not need to take an additional dose, but you should continue with the next scheduled dose.

drug interactions

1. CYP3A inhibitors: such as fluconazole, etc., the simultaneous use with tazetostat can increase the steady-state AUCO-8h of tazetostat by 3.1 times and Cmax by 2.3 times.

2. Gastric acid reducing agents: For example, omeprazole, combined with tazetostat can increase the patient's steady-state AUCO-8h of tametostat by 26% and Cmax by 25%. It is not expected to have clinically relevant effects.

3. CYP3A substrates: such as midazolam, etc., combined with tazerestat can reduce midazolam AUCO12h by 40% and Cmax by 21%.

References:

Gounder M, Schöffski P, Jones RL, Agulnik M, Cote GM, Villalobos VM, Attia S, Chugh R, Chen TW, Jahan T, Loggers ET, Gupta A, Italiano A, Demetri GD, Ratan R, Davis LE, Mir O, Dileo P, Van Tine BA, Pressey JG, Lingaraj T, Rajarethinam A, Sierra L, Agarwal S, Stacchiotti S. Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARB1: an international, open-label, phase 2 basket study. Lancet Oncol. 2020 Nov;21(11):1423-1432. doi: 10.1016/S1470-2045(20)30451-4. Epub 2020 Oct 6. PMID: 33035459.

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