Activity of Nab-sirolimus in Malignant Perivascular Epithelioid Cell Tumors

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In the phase II AMPECT trial reported in the Journal of Clinical Oncology, Wagner et al found that the mTOR inhibitor nab-sirolimus produced a substantial rate of durable responses and a high disease control rate in patients with malignant perivascular epithelioid cell tumors.

As stated by the investigators, “Malignant perivascular epithelioid cell tumor is a rare aggressive sarcoma, with no approved treatment. To our knowledge, this phase II, single-arm, registration trial is the first prospective clinical trial in this disease….”

Study Details

The trial enrolled 35 patients between April 2016 and November 2018 at nine U.S. centers. Patients received nab-sirolimus at 100 mg/m2 intravenously once weekly for 2 weeks in 3-week cycles until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by 6 months on independent radiology review.


Among 31 patients evaluable for efficacy, objective response by 6 months was observed in 12 (39%, 95% confidence interval [CI] = 22%–58%), with complete response observed in 1. An additional 16 patients (52%) had stable disease; 9 had stable disease for ≥ 12 weeks, yielding a disease control rate of 71%. Response occurred within 6 weeks in 67% of responders. Median duration of response was not reached after a median follow-up of 2.5 years; at last follow-up, 7 of 12 responders remained on treatment (range = 5.6–47.21 months). Among 25 patients with tumor profiling, response was observed in 8 (89%) of 9 with a TSC2 mutation vs 2 (13%) of 16 without a TSC2 mutation (P < .001).


  • Objective response was observed in 39% of patients, and disease control was observed in 71%.
  • Median duration of response was not reached.

Median progression-free survival was 10.6 months (95% CI = 5.5 months–not reached) and median overall survival was 40.8 months (95% CI = 22.2 months–not reached).

Adverse Events

Among 34 patients evaluable for safety, the most common nonhematologic treatment-related adverse events of any grade were mucositis (79%), fatigue (59%), and rash (56%); the most common hematologic events of any grade were anemia (47%) and thrombocytopenia (32%). The most common treatment-related grade 3 adverse events were mucositis (18%), anemia (12%), and hyperglycemia (9%); no grade 4 or 5 events were observed. Noninfectious pneumonitis occurred in 18% of patients (all grade 1 or 2). Treatment-related serious adverse events occurred in 24%, most commonly metabolism/nutrition disorders (4 of 12 total events) and gastrointestinal disorders (3 events). Treatment-related adverse events led to discontinuation of treatment in two patients (due grade 2 anemia and grade 1 cystitis, respectively). 

The investigators concluded, “Nab-sirolimus is active in patients with malignant perivascular epithelioid cell tumors. The response rate, durability of response, disease control rate, and safety profile support that nab-sirolimus represents an important new treatment option for this disease.”

Andrew J. Wagner, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by an FDA Office of Orphan Products Development grant and by Aadi Bioscience. For full disclosures of the study authors, visit

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