On January 23, 2020, the FDA accelerated the approval of tazemetostat (Tazverik; Epizyme Inc), an EZH2 methyltransferase blocker, for the treatment of patients aged ≥16 years with metastatic or locally advanced epithelioid sarcoma (a subtype of soft-tissue sarcoma) that is not eligible for complete resection. Tazemetostat received an orphan drug designation for this indication.
“Epithelioid sarcoma accounts for less than one percent of all soft-tissue sarcomas,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Until today, there were no treatment options specifically for patients with epithelioid sarcoma. The approval of Tazverik provides a treatment option that specifically targets this disease.”
Epithelioid sarcoma usually begins in the soft-tissue area under the skin of an extremity, although it can start in other areas of the body. For patients with localized disease, surgery is the standard treatment; chemotherapy or radiation may also be used, but the likelihood of progression to metastatic disease is high with these treatments; approximately 50% of people have metastatic disease at the time of diagnosis.
The approval of tazemetostat was based on a clinical trial of 62 patients with metastatic or locally advanced epithelioid sarcoma. Patients received 800 mg of tazemetostat twice daily until disease progression or unacceptable toxicity. The primary end point was overall response rate (ORR).
The ORR was 15%, consisting of 1.6% complete responses and 13% partial responses. Of the 9 patients who had a response, 6 (67%) patients had a response lasting >6 months.
The most common adverse events were pain, fatigue, nausea, decreased appetite, vomiting, and constipation. Tazemetostat therapy is associated with an increased risk for secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, and acute myeloid leukemia, and the drug can also cause harm to a fetus.