Phase II Trial of nab- Sirolimus in Patients With Advanced Malignant Perivascular Epithelioid Cell Tumors (AMPECT): Long-Term Efficacy and Safety Update

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.nab-Sirolimus is approved in the United States for the treatment of metastatic or locally advanced malignant perivascular epithelioid cell tumor (PEComa) on the basis of the primary analysis results of the phase II Advanced Malignant Perivascular Epithelioid Cell Tumors (AMPECT) trial (ClinicalTrials.gov identifier: NCT02494570). Results from the primary analysis were previously published; however, the median duration of response (mDOR) had not been reached at that time. Here, 3 years after the primary analysis, we report final efficacy and safety data (data cutoff: April 29, 2022). At study completion, the confirmed overall response rate (by independent radiologist review using RECIST v1.1) was 38.7% (95% CI, 21.8 to 57.8), with an additional converted confirmed complete response (n = 2). Median progression-free survival remained the same at 10.6 months (95% CI, 5.5 to 41.2). The mDOR was reached at 39.7 months (95% CI, 6.5 to not reached [NR]), and the median overall survival at completion was 53.1 months (95% CI, 22.2 to NR). The most common treatment-related adverse events (TRAEs) were stomatitis (82.4%) and fatigue and rash (each 61.8%). No new or unexpected adverse events occurred, and no grade ≥4 TRAEs were reported. These results highlight the long-term clinical benefit of nab-sirolimus in patients with advanced malignant PEComa, with a DOR of >3 years.

FIG 1.

Tumor responses to nab-sirolimus in patients with PEComa per RECIST v1.1. (A) Spider plot showing changes in the sum of target tumor measurements over time. Arrowheads indicate patients who were still on treatment at the time of the 3.5-year follow-up. (B) Waterfall plot of the best overall change from baseline in the sum of target tumor measurements, evaluated at the 3.5-year follow-up. PEComa, perivascular epithelioid cell tumor.

FIG A1.

Best overall response among patients with at least one dose reduction (n = 14). Best overall responses are based on independent radiologist review; however, treatment decisions were made by the treating investigator on the basis of radiology review and clinical symptoms. ^aThe patient had unconfirmed PR and discontinued therapy because of an AE without a confirmatory scan. AE, adverse event; PR, partial response.