nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors

Author:

Wagner Andrew J.1ORCID,Ravi Vinod2ORCID,Riedel Richard F.3ORCID,Ganjoo Kristen4,Van Tine Brian A.5ORCID,Chugh Rashmi6ORCID,Cranmer Lee7,Gordon Erlinda M.8,Hornick Jason L.9ORCID,Du Heng9ORCID,Grigorian Berta10,Schmid Anita N.10,Hou Shihe10,Harris Katherine10,Kwiatkowski David J.9ORCID,Desai Neil P.10,Dickson Mark A.11

Affiliation:

1. Dana-Farber Cancer Institute and Harvard Medical School, Boston MA

2. MD Anderson Cancer Center, Houston, TX

3. Duke Cancer Institute, Durham, NC

4. Stanford University, Stanford, CA

5. Washington University in St Louis, St Louis, MO

6. University of Michigan, Ann Arbor, MI

7. University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA

8. Sarcoma Oncology Center, Santa Monica, CA

9. Brigham and Women's Hospital, Boston, MA

10. Aadi Bioscience Inc, Pacific Palisades, CA

11. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY

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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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