nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors

J Clin Oncol. 2021 Nov 20;39(33):3660-3670. doi: 10.1200/JCO.21.01728. Epub 2021 Oct 12.

Abstract

Purpose: Malignant perivascular epithelioid cell tumor (PEComa) 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, investigating the safety and efficacy of the mammalian target of rapamycin inhibitor nab-sirolimus (AMPECT, NCT02494570).

Patients and methods: Patients with malignant PEComa were treated with nab-sirolimus 100 mg/m2 intravenously once weekly for 2 weeks in 3-week cycles. The primary end point was objective response rate evaluated by independent radiology review. Key secondary end points included duration of response, progression-free survival, and safety. A key exploratory end point was tumor biomarker analysis.

Results: Thirty-four patients were treated (safety evaluable), and 31 were evaluable for efficacy. The overall response rate was 39% (12 of 31; 95% CI, 22 to 58) with one complete and 11 partial responses, 52% (16 of 31) of patients had stable disease, and 10% (3 of 31) had progressive disease. Responses were of rapid onset (67% by week 6) and durable. Median duration of response was not reached after a median follow-up for response of 2.5 years, with 7 of 12 responders with treatment ongoing (range, 5.6-47.2+ months). Twenty-five of 31 patients had tumor mutation profiling: 8 of 9 (89%) patients with a TSC2 mutation achieved a confirmed response versus 2 of 16 (13%) without TSC2 mutation (P < .001). The median progression-free survival was 10.6 months (95% CI, 5.5 months to not reached), and the median overall survival was 40.8 months (95% CI, 22.2 months to not reached). Most treatment-related adverse events were grade 1 or 2 and were manageable for long-term treatment. No grade ≥ 4 treatment-related events occurred.

Conclusion: nab-Sirolimus is active in patients with malignant PEComa. 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Albumins / chemistry
  • Albumins / metabolism*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Neoplasm Metastasis
  • Perivascular Epithelioid Cell Neoplasms / drug therapy*
  • Perivascular Epithelioid Cell Neoplasms / pathology
  • Prognosis
  • Prospective Studies
  • Sirolimus / chemistry
  • Sirolimus / therapeutic use*
  • Survival Rate

Substances

  • Albumins
  • Antibiotics, Antineoplastic
  • Sirolimus

Associated data

  • ClinicalTrials.gov/NCT02494570