FDA OKs First Drug for Aggressive, Ultra-Rare Sarcoma

The FDA approved nab-sirolimus (Fyarro) on Tuesday 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 for 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 approved drug for advanced malignant PEComa, an aggressive sarcoma with a poor prognosis and few treatment options, will provide physicians with a new weapon,” said lead investigator Andrew Wagner, MD, PhD, of Dana-Farber Cancer Institute in Boston, in a 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,” added Wagner. “This is a drug that will be welcomed by the physician community.”

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

Prescribing information for the agent includes warnings and precautions related to stomatitis, myelosuppression, infections, hypokalemia, hyperglycemia, interstitial lung disease, hemorrhage, hypersensitivity, embryo-fetal toxicity, 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 decreased weight (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 hemoglobin (6%), and increased lipase (6%).