On November 22, 2021, sirolimus protein-bound particles for injectable suspension (albumin-bound) was approved for treatment of adults with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor.¹

Supporting Efficacy Data

Approval was supported by findings in the multicenter ­AMPECT trial (ClinicalTrials.gov identifier NCT02494570), in which 31 patients received sirolimus protein-bound particles at 100 mg/m² on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity.

Objective response on blinded independent central review was observed in 12 patients (39%, 95% confidence interval [CI]  = 22%–58%), including a complete response in 2 patients. Median duration of response was not reached (95% CI = 6.5 months to not estimable; range = 5.6–55.5+ months); responses lasting more than 12 and more than 24 months were observed in 67% and 58% of responders.

How It Is Used

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 toxicity.

Product labeling provides instructions on dosage modification, including dose reduction, for adverse reactions including stomatitis, anemia, thrombocytopenia, neutropenia, infections, hypokalemia, hyperglycemia, interstitial lung disease/pneumonitis, hemorrhage, and other grade 3 or 4 adverse reactions. Dosage modification instructions are provided for use in mild or moderate hepatic impairment and for concomitant use with moderate or weak CYP3A4 inhibitors (such as cimetidine, amiodarone, erythromycin, and fluconazole) and for strong CYP3A4 and P-glycoprotein inhibitors and inducers (such as clarithromycin, diltiazem, ketoconazole, rifampicin, and St. John’s wort).

Safety Profile

Among 34 patients receiving sirolimus protein-bound particles in the AMPECT trial, the most common (≥ 30%) adverse events of any grade were stomatitis (79%), fatigue (68%), rash (68%), infection (59%), nausea (50%), edema (50%), diarrhea (47%), musculoskeletal pain (47%), decreased weight (47%), decreased appetite (44%), cough (35%), vomiting (32%), and dysgeusia (32%). The most common grade 3 or 4 adverse events included stomatitis (18%), infections (12%), abdominal pain (6%), and dehydration (6%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (21%), decreased potassium (12%), and increased glucose (12%).

Serious adverse events occurred in 41% of patients, most commonly infection (12%) and abdominal pain, dehydration, and upper gastrointestinal hemorrhage (6% each). Adverse events led to discontinuation of treatment in 9%, due to pneumonitis, anemia, and noninfective cystitis. A fatal adverse event, upper gastrointestinal hemorrhage, occurred in one patient.

Sirolimus protein-bound particles has warnings/precautions for stomatitis, myelosuppression, infections, hypokalemia and hyperglycemia, interstitial lung disease/noninfectious pneumonitis, hemorrhage, hypersensitivity reactions, embryofetal toxicity, male infertility, and live vaccines. Patients should be advised not to breastfeed while receiving sirolimus protein-bound particles. The agent is contraindicated in patients with a history of severe hypersensitivity to sirolimus, other rapamycin derivatives, or albumin. 

REFERENCE

1. Fyarro (sirolimus protein-bound particles for injectable suspension; albumin-bound), for intravenous use prescribing information, Aadi Bioscience, Inc. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213312lbl.pdf. Accessed November 30, 2021.