FDA Approves Tazemetostat (Tazvenik) for Rare Sarcoma
For the first time, a drug has been approved by the US Food and Drug Administration (FDA) for the treatment of epithelioid sarcoma, a rare subtype of soft tissue sarcoma that occurs in young adults.
The drug is tazemetostat (Tazvenik, Epizyme Inc), and it acts as an inhibitor of EZH2 methyltransferase. It is indicated for the treatment of metastatic or locally advanced epithelial sarcoma in cases in which complete resection is not possible.
This is the first drug with that mechanism of action, and it is the first to be indicated for epithelioid sarcoma, the agency noted.
The FDA granted an accelerated approval on the basis of response rate data from an open-label clinical trial in 62 patients. All patients received tazemetostate 800 mg twice daily. The overall response rate was 15% (9 of 62 patients), with 1.6% of patients having a complete response and 13% having a partial response. Among the nine patients who had a response, six (67%) patients had a response that lasted 6 months or longer.
The most common side effects were pain, fatigue, nausea, decreased appetite, vomiting, and constipation. Tazemetostate may increase the risk for secondary malignancies, the agency noted.
When these data were discussed at a recent meeting of the FDA’s Oncologic Drugs Advisory Committee, “the committee voted unanimously that the benefits of the drug outweighed the risks,” commented 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,” he added. This approval “provides a treatment option that specifically targets this disease.”
Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial. The manufacturer is now conducting a global, randomized, controlled confirmatory trial to assess the combination of tazemetostat plus doxorubicin compared with doxorubicin plus placebo as a frontline treatment for epithelial sarcoma.
Rare Tumor, Often Metastatic on Diagnosis
Epithelioid sarcoma is rare. It accounts for fewer than 1% of all sarcomas and is diagnosed in 150 to 200 people in the United States each year.
The diagnosis can be easily missed. The disease often presents as a hard lump in soft tissue, such as under the skin in the extremities or in the abdomen or groin, in young adults (aged 20–30 years) who are apparently healthy.
Surgery is usually considered if the tumor is localized in one part of the body. Chemotherapy and radiotherapy may also be given, the FDA notes. However, there is a high likelihood of local and regional spread of the disease even with treatment, and approximately 50% of patients have metastatic disease at the time of diagnosis. Metastatic disease is considered life-threatening, the agency notes.
“There are limited therapeutic options for treating patients with epithelioid sarcoma, who struggle with high rates of recurrence and toxicities associated with currently used therapies,” said Gary K. Schwartz, MD, chief of hematology and oncology at Columbia University and New York–Presbyterian Hospital, New York City. He was the lead investigator of the clinical trial of tazemetostat.
The results from that trial “support its potential to provide clinically meaningful and durable responses, and tolerability,” he said in a statement.
“For people with epithelioid sarcoma, an aggressive life-threatening cancer that affects young adults, having new treatment options can offer much needed hope,” added Denise Reinke, MS, NP, MBA, president and chief executive officer of the Sarcoma Alliance for Research Through Collaboration (SARC) and cofounder of the Sarcoma Coalition.
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