On November 22, 2021, the FDA approved sirolimus protein-bound particles for injectable suspension (albumin-bound [Fyarro; Aadi Bioscience]) for adults with locally advanced, unresectable or metastatic malignant perivascular epithelioid-cell tumor (PEComa), a rare type of mesenchymal tumors that can occur in any body site.
This FDA approval was based on a multicenter, single-arm clinical trial of 31 patients with locally advanced, unresectable or metastatic malignant PEComa. Patients received sirolimus protein-bound particles on days 1 and 8 of each 21-day cycle, until disease progression or unacceptable adverse events.
The main end points were overall response rate (ORR) and duration of response (DOR). The ORR was 39% (95% confidence interval [CI], 22%-58%), which included 2 patients with complete responses. The median DOR was not reached (95% CI, 6.5 months-not estimable). Of the 39% of patients who had a response, 67% had a response lasting >12 months, and 58% had a response lasting >24 months.
The most common (≥30%) adverse events were stomatitis, fatigue, rash, infection, nausea, edema, diarrhea, musculoskeletal pain, decreased weight, decreased appetite, cough, vomiting, and dysgeusia. The most common (≥6%) grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased glucose, decreased potassium, decreased phosphate, decreased hemoglobin, and increased lipase.
The recommended dosage is 100 mg/m2, administered as an intravenous infusion over 30 minutes on days 1 and 8 of each 21-day cycle, until disease progression or unacceptable side effects.