他泽司他靶向药的治疗效果与用药疗程？

Tazerestat targeted drug has a significant effect on relapsed or refractory follicular lymphoma and epithelioid sarcoma. It can increase the objective response rate and improve the quality of life of patients. However, since each patient's situation is different, the course of medication also varies from person to person, and the specific course of treatment should be clarified according to the doctor's instructions.

Introduction to the targeted drug tazerestat

It is the first small molecule enhancer of zeste homologue 2 inhibitor. It received accelerated approval in the United States in January 2020 for the treatment of adults and adolescents aged ≥16 years with locally advanced or metastatic epithelioid sarcoma that is not suitable for complete resection.

Tazetostat, developed in partnership with Epizyme and Eisai, is the first therapy approved specifically for the treatment of epithelioid sarcoma in the United States. Tazemetostat is also in clinical development in several countries around the world for the treatment of several other tumor types, including diffuse large B-cell lymphoma and mesothelioma.

Tazerestat Dosing Guide

The recommended dosage regimen of tazerestat is 800 mg twice daily, administered orally with or without food, until disease progression or unacceptable toxicity.

Tazerestat medication regimen

The medication regimen of tazerestat usually needs to be customized by the doctor based on the patient's specific condition, treatment response and tolerance.

In the treatment of epithelioid sarcoma, there is generally no fixed course length. Instead, administration is continued based on the patient's clinical response and disease control until disease progression or unacceptable toxicity occurs.

In the treatment of lymphoma, long-term maintenance treatment is usually performed until the disease worsens or intolerable side effects occur.

Therefore, the initiation, duration, dose adjustment, and when to stop the specific course of tazerestat treatment require doctors to make personalized settings based on the specific conditions of the patient, and adjust the treatment plan through regular evaluation during the treatment process.

Efficacy of tazerestat in the treatment of follicular lymphoma

Purpose: In the tazerestat E7438-G000-101 relapsed/refractory (R/R) follicular lymphoma (FL) trial, the efficacy of mutant (MT) ezh 2 was significantly better than that of wild type (WT). However, clinical differences may have contributed to this conclusion. This study was designed to evaluate outcomes after minimizing differences in baseline characteristics.

Methods: Propensity scores for each participant in the WT and MT conditions were generated based on their likelihood of being selected. Participants were matched using the 1:1 nearest neighbor method.

Results: The propensity-matched sample included 56 participants. The objective response rates of the WT group and MT group before matching were 35% and 69% respectively, and after matching the objective response rates of the WT group and MT group were 50% and 71% respectively. The median progression-free survival values ​​before matching were 11.1 and 13.8 months in the WT group and MT group, respectively, and 14.3 and 14.8 months in the WT and MT matching groups, respectively.

Conclusion: This analysis suggests that the efficacy results of tazerestat observed in WT EZH2 R/R FL participants may be similar to those in MT participants if the two cohorts were more closely matched.

Efficacy of tazerestat in the treatment of malignant pleural mesothelioma

Background: There are few treatment options for malignant pleural mesothelioma. Tazerestat has shown antitumor activity in a variety of hematological cancers and solid tumors.

Methods: An open-label, single-arm phase 2 study was conducted at 16 hospitals in France, the UK and the US. Eligible patients were 18 years of age or older, had malignant pleural mesothelioma of any histology, were relapsed or refractory after treatment with at least one pemetrexed-containing regimen, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had a life expectancy greater than 3 months. In part 1 of the study, participants received tazerestat 800 mg orally once on day 1 and then twice daily starting on day 2. In Part 2, participants received tazerestat 800 mg orally twice daily starting on Day 1 of Cycle 1 in a two-stage Green-Dahlberg design. Tazetostat is administered in 21-day cycles for approximately 17 cycles.

The primary endpoint of Part 1 is the pharmacokinetics of tazerestat and its metabolites on day 15 after taking 800 mg of tazerestat, as measured by the maximum serum concentration (Cmax) assessed in all patients enrolled in part 1, reaching Cm ax (Tmax), the area under the concentration-time curve to day 15 (AUC) and the area under the curve extrapolated from time 0 to infinity (AUC0-∞), and the half-life of tazerestat (t1/2).

The primary endpoint of Part 2 is disease control rate (proportion of patients with complete response, partial response, or stable disease) at week 12 in patients with malignant pleural mesothelioma.

Results: A total of 74 patients were enrolled and treated with tazerestat, of which 73 (99%) had BAP1-inactivated tumors. In Part 1, after repeated administration of tazerestat at steady state on Day 15 of Cycle 1, the mean Cmax was 829 ng/mL, the median Tmax was 2 h, the mean AUC0-twas 3310 hng/mL, and the mean AUC0-∞ was 3180 h. ng/mL (46±6%), geometric mean t1/2 of 3±1h6 After a median follow-up of 35±9 weeks, the disease control rate in patients with BAP1-inactivated malignant pleural mesothelioma in Part 2 was 54%. No patient had a confirmed complete response.

Further refinement of biomarkers of tazerestat activity in malignant pleural mesothelioma following BAP1 inactivation will help identify tumor subpopulations most likely to derive long-term benefit or shrinkage from this therapy.

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