Tazemetostat– A Drug review

Abstract

Epithelioid sarcoma affects three in 10 million people, usually teenagers and young adults. Tumours grow under the skin of the extremities or they can affect the trunk, head, or neck. It grows slowly, but can infiltrate surrounding tissues, later on, it frequently metastasis to lymph nodes. For advanced case, doxorubicin-based chemotherapy regimen is recommended. In January 2020, FDA approved the first-in-class, small molecule enhancer of zeste homolog 2 (EZH2) inhibitor, tazemetostat (Tazverik) to treat adults and paediatric patients aged 16 years and older with locally advanced or metastatic epithelioid sarcoma not suitable for complete resection. The recommended dosage is 800 mg twice daily until disease progression or unacceptable toxicity. The first-in-human study of tazemetostat was a phase 1 open-label multi-centered dose-escalation study. Tazemetostat is having an oral bioavailability of approximately 33%. Apparent volume of distribution at steady-state (Vss/F) is 1230 L (46%) with 88% bound to human plasma proteins. Metabolism takes place via CYP3A. 15% and 79% of radioactivity is excreted through urine and feces respectively. ≥20% of the adverse reactions and above was fatigue, pain, constipation, nausea, anorexia and vomiting. This article summarizes the history, chemistry, physical properties, mechanism of action, indications, and drug–drug interactions of tazemetostat and we also discuss briefly the results of various clinical trials.