The U.S. Food and Drug Administration (FDA) has approved FYARRO™ (sirolimus protein-bound particles for injectable suspension) (albumin-bound) for intravenous use for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa). FYARRO is the first and only FDA-approved treatment for advanced malignant PEComa in adults.
About Malignant PEComa
Advanced malignant PEComa, defined by the World Health Organization as ‘mesenchymal tumors composed of distinctive cells that show a focal association with blood-vessel walls and usually express both melanocytic and smooth muscle markers,’ are a rare subset of soft-tissue sarcomas, with an undefined cell of origin. Malignant PEComas may arise in almost any body site (typically the uterus, retroperitoneum, lung, kidney, liver, genitourinary, and gastrointestinal tract with a female predominance) and can have an aggressive clinical course including distant metastases and ultimately death. Malignant PEComas have been shown to frequently harbor mutations in the TSC1 and/or TSC2 genes that result in the activation of mTOR pathway making it a rational therapeutic target for this disease.
About FYARRO™
FYARRO is an mTOR inhibitor indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).
In the Phase 2 clinical trial leading to FDA approval the overall response rate to Fyarro was 39% with 2 patients achieving a complete response. The median duration of response was not reached with a median follow-up of 36 months. Among patients responding to treatment, 92% had a response lasting greater than or equal to 6 months and 58% had a response lasting greater than or equal to 2 years.
At the 2024 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer clinical study results in ptients with PEComa of gynecologic or peritoneal origin were reported. Patients experienced rapid, durable responses when treated with Fyarro on the phase 2 AMPECT trial (NCT02494570) presented by Thomas Herzog, MD,
An overall response rate of 37.5% among 16 female patients with malignant PEComa in uterine, ovarian, pelvic, and retroperitoneal sites, regardless of TSC1/TSC2 mutation status was reported, and 4 of 16 patients (25%) experienced stable disease for at least 12 weeks. The median duration of response was 39.7 months, and the median overall survival was 53.1 months.
Nab-Sirolimus remains the first and only FDA-approved treatment for locally advanced or metastatic malignant unresectable PEComa. The agent was approved in this intent-to-treat population in November 2021.2
Side effects associated with FYARRO include mouth sores, low blood counts, rash, fatigue and infection.
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References
Herzog T, Dockery L, Dickson M, et al. Response to treatment with nab-sirolimus in patients with perivascular epithelioid cell sarcoma (PEComa) of gynecologic or peritoneal origin: subgroup analysis from AMPECT. Presented at: Society of Gynecologic Oncology 2024 Annual Meeting on Women’s Cancer, March 16-18, 2024. San Diego, CA.
FDA approves sirolimus protein-bound particles for malignant perivascular epithelioid cell tumor. News release. FDA. November 22, 2021. Accessed March 17, 2024. https://tinyurl.com/4wx99snr
