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nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors
Andrew J Wagner1, Vinod Ravi2, Richard F Riedel3
1Dana-Farber Cancer Institute and Harvard Medical School, Boston MA.
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.
Insights
This study shows nab-sirolimus is an effective treatment for malignant perivascular epithelioid cell tumors (PEComa), demonstrating significant response rates and durable outcomes in a rare sarcoma. The drug is well-tolerated, offering a new therapeutic option.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Malignant perivascular epithelioid cell tumor (PEComa) is a rare and aggressive sarcoma lacking approved treatments.
- This study addresses the unmet need for effective therapies in malignant PEComa.
Purpose of the Study:
- To investigate the safety and efficacy of nab-sirolimus, a mammalian target of rapamycin inhibitor, in patients with malignant PEComa.
- This represents the first prospective clinical trial for this rare disease.
Main Methods:
- A phase II, single-arm, registration trial (AMPECT, NCT02494570) was conducted.
- Patients received nab-sirolimus intravenously weekly for two weeks in 3-week cycles.
- Objective response rate, duration of response, progression-free survival, safety, and tumor biomarkers were assessed.
Main Results:
- An overall response rate of 39% was observed in 31 efficacy-evaluable patients, with durable responses.
- Median progression-free survival was 10.6 months and median overall survival was 40.8 months.
- Patients with TSC2 mutations showed significantly higher response rates (89%) compared to those without (13%).
- Nab-sirolimus was generally well-tolerated with manageable adverse events.
Conclusions:
- Nab-sirolimus demonstrates significant activity in malignant PEComa patients.
- The drug's efficacy, response durability, and safety profile establish it as a promising new treatment option.
- Tumor biomarker analysis, particularly TSC2 mutations, may predict treatment response.
