FDA approves first drug for aggressive and ultra-rare sarcoma

The FDA on Tuesday approved nab-sirolimus (Fyarro) for the treatment of malignant perivascular epithelioid cell tumors (PEComa), a rare and aggressive form of sarcoma.

Nab-sirolimus, an albumin-bound mTOR inhibitor, is indicated in patients with locally advanced unresectable or metastatic malignant PEComa. These ultra-rare soft tissue sarcomas can occur in virtually any part of the body and have an extremely aggressive clinical course, with an estimated median survival of 12 to 16 months.

Support for approval came from the AMPECT trial, which involved 31 patients with malignant PEComa. Nab-sirolimus demonstrated an overall response rate of 39% (95% CI 22-58) on independent review, including two complete responses (7%).

“The approval of Fyarro, the first drug approved for advanced malignant PEComa, an aggressive sarcoma with a poor prognosis and few treatment options, will provide physicians with a new weapon,” said lead researcher Andrew Wagner, MD, PhD, of Dana-Farber Cancer Institute in Boston, in a press release from drugmaker Aadi Bioscience.

“In our AMPECT trial, Fyarro demonstrated durable responses in mTOR inhibitor-naive patients with locally advanced unresectable or metastatic PEComa, with an acceptable and manageable safety profile,” Wagner added. “It is a drug that will be well received by the medical community.”

With a median follow-up of 36 months, the median duration of response to nab-sirolimus was not reached in the phase II study (range 5.6 to 55.5+ months). Of the respondents, 92% had a response of at least 6 months, two-thirds had a response of one year or more and 58% had a response lasting 2 years or more.

The agent’s prescribing information includes warnings and precautions for stomatitis, myelosuppression, infections, hypokalaemia, hyperglycemia, interstitial lung disease, hemorrhage, hypersensitivity, embryonic toxicity -fetal and male infertility.

Common adverse events with nab-sirolimus in AMPECT included stomatitis (79%); fatigue and rash (68% each); infection (59%); nausea and edema (50% each); diarrhea, musculoskeletal pain and weight loss (47% each); decreased appetite (44%); cough (35%); and vomiting and dysgeusia (32% each).

Common grade 3/4 laboratory abnormalities included decreased lymphocytes (21%), increased glucose (12%), decreased potassium (12%), decreased phosphate (9%), decreased blood hemoglobin (6%) and an increase in lipase (6%).

  • Mike Bassett is a writer specializing in oncology and hematology. He is based in Massachusetts.

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