Rapid, durable responses with nab-sirolimus in gynaecologic or peritoneal PEComa

Treatment with the mammalian target of rapamycin inhibitor nab-sirolimus yields rapid and durable responses among patients with perivascular epithelioid sarcoma (PEComa) of gynaecologic or peritoneal origin in a subgroup analysis of the phase II AMPECT trial.

An overall response rate (ORR) of 37.5 percent (95 percent confidence interval [CI], 15.2–64.6) was observed among 16 female patients with malignant PEComa in uterine, ovarian, pelvic, and retroperitoneal sites, regardless of TSC1/TSC2 mutation status. “This was similar to the 38.7 percent ORR observed in the overall population,” reported study investigator Dr Thomas Herzog from the University of Cincinnati Cancer Center in Cincinnati, Ohio, US at SGO 2024.

He added that the disease control rate (DCR) in the subgroup was 62.5 percent, not far from the 71 percent DCR observed in the overall population. Four of the 16 patients had a stable disease for 12 weeks.

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.

As for safety, the most common treatment-related adverse events (TRAEs) were stomatitis (81 percent), fatigue (63 percent), oedema (56 percent), maculopapular rash (56 percent), diarrhoea and nausea (50 percent each).

Sixty-three percent experienced grade 3 TRAEs, which included stomatitis (25 percent), hyperglycaemia (13 percent), hypokalaemia (13 percent), increased amylase (6 percent), vomiting, and diarrhoea (6 percent each). No new or unexpected adverse events occurred, and no grade 4 or 5 TRAEs were reported.

TRAEs led to dose delay in 63 percent of the patients, dose reduction in 31 percent, and treatment discontinuation in 6 percent.

FDA-approved therapy

Nab-sirolimus is FDA-approved for adult patients with metastatic or locally advanced malignant PEComa, based on the primary analysis of the multicentre, single-arm, phase II AMPECT trial involving 31 patients. [J Clin Oncol 2021;39:3660-3670]

Patients received nab-sirolimus 100 mg/m² intravenously once weekly for 2 weeks in 3-week cycles until disease progression or unacceptable toxicity. 

The ORR to nab-sirolimus in the overall population was 39 percent, with one complete and 11 partial responses. This exceeded the prespecified lower-bound objective response rate of 15 percent, below which the regimen would be considered no more active than standard doxorubicin-based chemotherapy. Responses were rapid and durable.

The current subgroup analysis evaluated 16 female patients from the overall population of AMPECT. The median age of the patients was 61.5 years. Nine patients were White, 3 were Black, and 12 were considered non-Hispanic or Latino. [Herzog, T et al. SGO 2024]

“Nab-sirolimus represents an important treatment advance for patients with this rare disease,” said Herzog. “More studies are underway for nab-sirolimus in locally advanced unresectable or metastatic malignant PEComa.”

Malignant PEComa is a rare, aggressive soft tissue sarcoma with a poor prognosis and few treatment options. In the metastatic unresectable setting, overall survival ranges from 16 months with chemotherapy to 29 months with targeted therapy.