General Information

Fyarro (sirolimus protein-bound particles for injectable suspension) is an mTOR inhibitor.

Fyarro is specifically indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

Fyarro is supplied as a suspension for intravenous administration. The recommended dosage is 100 mg/m2 administered as an IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

Mechanism of Action

Fyarro (sirolimus protein-bound particles for injectable suspension) is an inhibitor of mechanistic target of rapamycin kinase (mTOR, previously known as mammalian target of rapamycin). mTOR, a serine threonine kinase, is downstream of the PI3K/AKT pathway, controls key cellular processes such as cell survival, growth, and proliferation, and is commonly dysregulated in several human cancers. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus-FKBP-12 complex binds to and inhibits activation of the mechanistic target of rapamycin complex 1 (mTORC1). Inhibition of mTOR by sirolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and in vivo studies.

Side Effects 

Adverse effects associated with the use of Fyarro may include, but are not limited to, the following:

• stomatitis
• fatigue
• rash
• infection
• nausea
• edema
• diarrhea
• musculoskeletal pain
• decreased weight
• decreased appetite
• cough
• vomiting
• dysgeusia
• Grade 3 to 4 laboratory abnormalities

Clinical Trial Results

FDA approval was based on AMPECT, a multicenter, single-arm clinical trial in 31 patients with locally advanced unresectable or metastatic malignant PEComa. Patients received FYARRO at a dose of 100 mg/m2 on Days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. The overall response rate as assessed by independent review was 39% (12/31) with 2 patients achieving a Complete Response after prolonged follow up. The median duration of response has not been reached with a median follow-up of 36 months, and a range of 5.6 to 55.5+ months and ongoing. Among responders, 92% had a response lasting greater than or equal to 6 months; 67% had a response lasting greater than or equal to 12 months; and 58% had a response lasting greater than or equal to 2 years.