On January 23, the U.S. Food and Drug Administration (FDA) granted accelerated approval to tazemetostat (Tazverik) for adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.
Richard Pazdur, MD
“Epithelioid sarcoma accounts for less than 1% of all soft-tissue sarcomas,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Until today, there were no treatment options specifically for patients with epithelioid sarcoma. The approval of tazemetostat provides a treatment option that specifically targets this disease. When we brought tazemetostat’s application to the Oncologic Drugs Advisory Committee last month, the committee voted unanimously that the benefits of the drug outweighed the risks.”
Tazemetostat blocks activity of the EZH2 methyltransferase.
Efficacy was investigated in a single-arm cohort (cohort 5) of a multicenter trial (Study EZH-202) in patients with histologically confirmed, metastatic, or locally advanced epithelioid sarcoma. Patients were required to have INI1 loss (detected using local tests) and an Eastern Cooperative Oncology Group performance status of 0–2. Patients received 800 mg of tazemetostat orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were confirmed overall response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1 (assessed by blinded independent central review), and duration of response.
The overall response rate for the 62 patients in cohort 5 was 15% (95% confidence interval = 7%–26%), with 1.6% having complete responses and 13% having partial responses; 67% of those responding had responses lasting 6 months or longer.
The most common adverse reactions (incidence ≥ 20% of patients) were pain, fatigue. nausea, decreased appetite, vomiting, and constipation.
The recommended tazemetostat dose is 800 mg taken orally twice daily with or without food.