Medical Oncology Unit 2, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Clin Cancer Res. 2020 Oct 15;26(20):5534-5538. doi: 10.1158/1078-0432.CCR-20-1191. Epub 2020 Jun 30.
Perivascular epithelioid cell tumors (PEComa) are rare mesenchymal neoplasms. mTOR inhibitors are the most active agents in PEComa and in patients progressing to mTOR inhibitors, other available therapies have limited benefit. Preclinical evidences showed a cross-talk between the mTOR pathway and estrogen receptor signaling. This provided a rationale for adding an antiestrogen treatment in female patients becoming resistant to mTOR inhibitors.
Since April 2018, female patients with advanced/metastatic PEComa progressing to mTOR inhibitors were treated with a combination of sirolimus and exemestane with or without LHRH analogue (based on menopausal status). This case series was retrospectively reviewed. Survival analyses were performed using the Kaplan-Meier method.
A total of seven consecutive patients treated with the combination of sirolimus and antiestrogen treatment were retrospectively reviewed. Six (86%) received a combination of sirolimus and exemestane, whereas one patient (14%) received a combination of sirolimus, exemestane, and triptorelin since in premenopausal status. After a median follow-up of 13.1 months, three patients (43%) experienced a partial response, three patients (43%) experienced a stabilization of disease, and one patient (14%) had disease progression with an overall response rate of 43% and a disease control rate of 86%.
In this small retrospective case series, the addition of antiestrogen treatment in female patients with advanced PEComa progressing to mTOR inhibitors resulted in a remarkable clinical benefit in a setting where no other options are available.
血管周上皮样细胞瘤（PEComa）是一种罕见的间叶性肿瘤。mTOR 抑制剂是治疗 PEComa 的最有效药物，对于进展至 mTOR 抑制剂的患者，其他可用的治疗方法获益有限。临床前证据表明 mTOR 通路与雌激素受体信号之间存在交叉对话。这为在对 mTOR 抑制剂耐药的女性患者中添加抗雌激素治疗提供了依据。
自 2018 年 4 月以来，对进展至 mTOR 抑制剂的晚期/转移性 PEComa 女性患者采用依维莫司联合来曲唑治疗，并根据绝经状态加用或不加促性腺激素释放激素类似物。本研究回顾性分析了这一系列病例。采用 Kaplan-Meier 法进行生存分析。
共回顾性分析了 7 例接受依维莫司联合抗雌激素治疗的连续患者。6 例（86%）接受依维莫司联合来曲唑治疗，1 例（14%）在绝经前状态下接受依维莫司、来曲唑和曲普瑞林联合治疗。中位随访 13.1 个月后，3 例（43%）患者部分缓解，3 例（43%）患者疾病稳定，1 例（14%）患者疾病进展，总缓解率为 43%，疾病控制率为 86%。
在本小样本回顾性病例系列研究中，在没有其他选择的情况下，在进展至 mTOR 抑制剂的晚期 PEComa 女性患者中添加抗雌激素治疗可显著获益。
