TAZEMOSTAT Receives FDA Approval for Advanced Epithelioid SARCOMA

On 23 January 2020, the US Food and Drug Administration (FDA) granted accelerated approval for patients over 16, unsuitable for complete resection, surgical removal, with metastatic or locally advanced epithelioid sarcoma , for treatment with tazemetostat (Tazverik).

Efficacy was studied in the multicenter EZH-202 trial's single-arm group, Cohort 5, with histologically confirmed metastatic or locally advanced epithelioid sarcoma. Tumors required the genetic abnormality loss of INI1(INI1-negative), and overall performance status had to be 0-2.

Patients received twice-daily 800 mg tazemetostat until progression or unacceptable adverse effects. Main efficacy endpoints were duration of response and overall response rate .

• In Cohort 5, among 62 patients, overall response was % 15: % 1.6 complete and % 13 partial responses.
• Of responders, % 67 had responses lasting 6 months or longer.

The most common (frequency ≥ 20) adverse effects were pain, fatigue, nausea, decreased appetite, vomiting, and constipation.

The recommended tazemetostat doseis twice daily, with or without food, 800 mg.

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This was “accelerated approval” based on overall response rate and duration. Continued approval may depend on clinical benefit confirmation and characterization in a confirmatory trial. FDA granted tazemetostat orphan drug designation.

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What Is Epithelioid Sarcoma?

The three most common soft tissue sarcomas are malignant fibrous histiocytoma, pleomorphic sarcoma, rhabdomyosarcoma, and liposarcoma, followed by much rarer types including epithelioid sarcoma, synovial sarcoma, clear cell tendon sarcoma, and alveolar soft part sarcoma.

Diagnosis of these usually slow-course rare sarcomas is often delayed. Another shared characteristic is their high likelihood of distant organ metastasis. Magnetic resonance imaging (MRI)is the most important imaging method for diagnosis, staging, surgical planning, and follow-up. Definitive diagnosis mainly uses histopathology, with immunoreactivity and genetic abnormalities such as INI1 loss also providing guidance.

Epithelioid sarcoma usually begins in soft tissue beneath the skin of the extremities, arms and legsbut can originate elsewhere.

Wide or radical surgery is the treatment foundation, as for other soft tissue sarcomas. Pre- or postoperative radiotherapy is often added, and systemic chemotherapy sometimes. Certain anatomical locations, postoperative recurrence, and distant metastasis indicate poor prognosis.

How Does Tazemetostat Work?

Tazemetostat regulates gene expression through epigenetic mechanisms as an anticancer drug. Mutations activating EZH2 are drivers in various cancers. Tazemetostat is a potent, selective EZH2 inhibitor , an oral small-molecule cancer drug. It blocks EZH2 methyltransferase enzyme activity that may help cancer cells grow.