Tazemetostat

Tazemetostat is an oral, selective inhibitor of EZH2, a histone methyltransferase that is part of the Polycomb repressive complex 2 (PRC2). By inhibiting EZH2, tazemetostat reduces trimethylation of histone H3 at lysine 27 (H3K27me3), which can alter gene expression and influence the growth and differentiation of certain cancer cells that depend on EZH2 activity. The drug is designed to target tumors with activating EZH2 mutations or aberrant EZH2-driven gene silencing.

Development and approval: Tazemetostat was developed by Epizyme and marketed under the brand name TAZVERIK. In the United States, the FDA has approved tazemetostat for adults with metastatic or locally advanced epithelioid sarcoma that is not amenable to safe surgical resection. A separate approval covers relapsed or refractory follicular lymphoma in adults with EZH2 activating mutations who have received at least two prior systemic therapies. These indications reflect the drug’s targeted mechanism in EZH2-altered cancers.

Administration and monitoring: The medication is taken by mouth, typically on a twice-daily schedule, with dosing adjusted for tolerance and adverse effects. Ongoing monitoring includes evaluation of blood counts and assessment for common chemotherapy-associated toxicities, such as fatigue, nausea, decreased appetite, and infections, as well as potential cytopenias.

Adverse effects and considerations: Reported adverse events commonly include fatigue, nausea, decreased appetite, vomiting, diarrhea, cough, and upper respiratory infections. Thrombocytopenia and anemia have been observed, and patients require regular laboratory monitoring. Tazemetostat is generally used in patients with specific EZH2-mutant tumors as part of a broader treatment strategy and is being studied in additional indications and combination regimens.