Nab-Sirolimus Delivers Durable Responses in PEComa Subgroups

Thomas Herzog, MD

Nab-sirolimus (Fyarro; ABI-009) delivered rapid and durable responses in patients with perivascular epithelioid sarcoma (PEComa), according to a subgroup analysis of the phase 2 AMPECT study (NCT02494570) presented by Thomas Herzog, MD, at the 2024 Society of Gynecologic Oncology Annual Meeting.¹

An overall response rate (ORR) of 37.5% (95% CI, 15.2%-64.6%) among 16 female patients with malignant PEComa in uterine, ovarian, pelvic, and retroperitoneal sites, regardless of TSC1/TSC2 mutation status was observed, and all responses were confirmed partial responses (PRs). Moreover, the disease control rate (DCR) in the subgroup was 62.5%, and 4 of 16 patients (25%) experienced stable disease for at least 12 weeks.

This subgroup comprised over half of the evaluable study population, and the ORR from this analysis was similar to the 38.7% ORR observed in the overall population evaluation. Additionally, the DCR in the overall population was 71%. Among all patients with malignant PEComa, the median duration of response (DOR) was 39.7 months, and the median overall survival (OS) was 53.1 months.

Regarding safety, 100% of patients experienced treatment-related adverse events (TRAEs) of any grade, while 63% of patients had a TRAE of grade 3. The most common any-grade TRAEs were stomatitis (81%), fatigue (63%), edema (56%), maculopapular rash (56%), diarrhea (50%), and nausea (50%). Grade 3 TRAEs included stomatitis (25%), hyperglycemia (13%), hypokalemia (13%), increased amylase (6%), vomiting (6%), and diarrhea (6%). There were no grade 4 or 5 TRAEs observed. TRAEs led to dose delay in 63% of patients, dose reduction in 31%, and treatment discontinuation in 6%.

About the Phase 2 AMPECT Study

The primary end point of the AMPECT study was ORR by independent review, and secondary end points included DOR, DCR, and safety/tolerability. Patients were eligible for enrollment if they were 18 or older, had an ECOG performance status of 0 to 1, had histologically confirmed malignant PEComa, had locally advanced or inoperable metastatic disease, and had not received treatment with a prior mTOR inhibitor.

A total of 16 female patients were evaluated in this subgroup analysis. The median age was 61.5 years (range, 39-78). Nine patients (56%) were White and 3 (19%) were Black. Twelve (75%) patients identified as not Hispanic or Latino. Of the overall population of 31 patients, 7 patients had a disease origin from the uterus, 1 from the ovary, 5 from the retroperitoneum, 3 from the pelvis, and 15 from another.

Patients were treated with 100 mg/m2 of intravenous nab-sirolimus on days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity were observed.

About PEComa and the Treatment Landscape

Nab-sirolimus is 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

Advanced malignant PEComas are associated with poor prognoses and typically demonstrate local invasion or metastases, according to the presentation from Herzog, University of Cincinnati Cancer Center.¹ In the metastatic unresectable setting, the median OS ranges from 16 months with chemotherapy to 29 months with targeted therapy. The presence of nab-sirolimus on the market represents an important treatment option as the standard of care for patients with this rare cancer.

According to Herzog, more studies are underway investigating nab-sirolimus to treat malignant PEComa mTOR-driven cancers of gynecologic origin.

REFERENCES:

1. 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.

2. 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