Role of Chemotherapy, VEGFR Inhibitors, and mTOR Inhibitors in Advanced Perivascular Epithelioid Cell Tumors (PEComas).

PURPOSE: Perivascular epitheliod cell tumors (PEComas) are rare mesenchymal neoplasms for which the role of systemic treatments is not established as there are no published prospective clinical trials or sufficiently large retrospective case series. The aim of this study is to clarify the activity of conventional chemotherapy and biological agents in advanced/metastatic PEComas. EXPERIMENTAL DESIGN: This was an observational, retrospective, international study that included patients with advanced/metastatic PEComa treated with systemic therapy at 5 European sarcoma reference centers and within the Italian Rare Cancer Network. Survival analyses were performed using the Kaplan-Meier method and the Cox hazards regression models. RESULTS: A total of 53 patients were included. Cytotoxic chemotherapy regimens were active only in a small proportion of PEComas. Gemcitabine-based regimens [objective response rate (ORR): 20%, median progression-free survival (PFS): 3.4 months] seemed to have the same activity of anthracycline-based regimens (ORR: 13%, median PFS: 3.2 months). Antiangiogenic agents resulted in disease stabilization in some patients, with a number having density changes/tissue response on imaging, with an ORR of 8.3% and a median PFS of 5.4 months. mTOR inhibitors were the most active agents, with an ORR of 41% and a median PFS of 9 months. CONCLUSIONS: Our study provides data for the selection of systemic therapy in patients with advanced/metastatic PEComa: mTOR inhibitors are the most active agents. Antiangiogenics and chemotherapy with gemcitabine-based regimens or anthracycline-based regimens are options in further line, but with a lower response rate and PFS.

Combination targeted therapy of VEGFR inhibitor, sorafenib, with an mTOR inhibitor, sirolimus induced a remakable response of rapid progressive Uterine PEComa.

Perivascular epithelioid cell tumor is a rare tumor. To date, there is no consensus of therapy to be recommended for unresectable disease. For a low incidence and a rarely curable disease, the finding of new therapy is essential. Here we report the first case of a patient with perivascular epithelioid cell tumor whose disease had a rapid progression after surgery and had a rapid remarkable response of combination therapy of a VEGFR inhibitor, sorafenib, with an mTOR inhibitor, sirolimus. This result may have potential to deliver a new treatment option and inhibiting the mTOR pathway combined with inhibiting the VEGF pathways may be a useful strategy for malignant PEComas.