Dana-Farber Cancer Institute and Harvard Medical School, Boston MA.
MD Anderson Cancer Center, Houston, TX.
J Clin Oncol. 2021 Nov 20;39(33):3660-3670. doi: 10.1200/JCO.21.01728. Epub 2021 Oct 12.
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 -sirolimus (AMPECT, NCT02494570).
Patients with malignant PEComa were treated with -sirolimus 100 mg/m 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.
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 mutation achieved a confirmed response versus 2 of 16 (13%) without mutation ( < .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.
-Sirolimus is active in patients with malignant PEComa. The response rate, durability of response, disease control rate, and safety profile support that -sirolimus represents an important new treatment option for this disease.
恶性血管周上皮样细胞瘤（PEComa）是一种罕见的侵袭性肉瘤，目前尚无批准的治疗方法。据我们所知，这项 II 期、单臂、注册临床试验是该疾病的首个前瞻性临床试验，研究了雷帕霉素靶蛋白抑制剂 -西罗莫司（AMPECT，NCT02494570）的安全性和疗效。
患有恶性 PEComa 的患者接受静脉注射 -西罗莫司 100 mg/m2，每周 1 次，每 2 周为 1 个周期，共 3 周。主要终点是独立影像学评估的客观缓解率。主要次要终点包括缓解持续时间、无进展生存期和安全性。一个关键的探索性终点是肿瘤生物标志物分析。
34 例患者接受了治疗（可进行安全性评估），31 例患者可进行疗效评估。总缓解率为 39%（31 例中的 12 例；95%CI，22%至 58%），包括 1 例完全缓解和 11 例部分缓解，52%（31 例中的 16 例）的患者疾病稳定，10%（31 例中的 3 例）的患者疾病进展。缓解迅速（67%在第 6 周）且持久。中位缓解后随访 2.5 年，中位缓解持续时间未达到，12 例缓解者中有 7 例仍在接受治疗（范围为 5.6-47.2+ 个月）。31 例患者中有 25 例进行了肿瘤突变分析：9 例（89%）携带 突变的患者获得了确认缓解，而 16 例（13%）无 突变的患者则无缓解（<0.001）。中位无进展生存期为 10.6 个月（95%CI，5.5 个月至未达到），中位总生存期为 40.8 个月（95%CI，22.2 个月至未达到）。大多数与治疗相关的不良事件为 1 级或 2 级，可长期治疗。未发生任何≥4 级的与治疗相关的不良事件。
-西罗莫司在恶性 PEComa 患者中具有活性。缓解率、缓解持续时间、疾病控制率和安全性支持 -西罗莫司是该疾病的一种重要新治疗选择。
