Addition of Antiestrogen Treatment in Patients with Malignant PEComa Progressing to mTOR Inhibitors

Clin Cancer Res. 2020 Oct 15;26(20):5534-5538. doi: 10.1158/1078-0432.CCR-20-1191. Epub 2020 Jun 30.

Abstract

Purpose: 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.

Experimental design: 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.

Results: 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%.

Conclusions: 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.

MeSH terms

  • Aged
  • Estrogen Antagonists / administration & dosage
  • Estrogen Antagonists / adverse effects
  • Everolimus / administration & dosage*
  • Everolimus / adverse effects
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Perivascular Epithelioid Cell Neoplasms / drug therapy*
  • Perivascular Epithelioid Cell Neoplasms / genetics
  • Perivascular Epithelioid Cell Neoplasms / pathology
  • Progression-Free Survival
  • Sarcoma / drug therapy*
  • Sarcoma / genetics
  • Sarcoma / pathology
  • Signal Transduction / drug effects
  • Sirolimus / administration & dosage*
  • Sirolimus / adverse effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics*
  • Triptorelin Pamoate / administration & dosage
  • Triptorelin Pamoate / adverse effects

Substances

  • Estrogen Antagonists
  • Triptorelin Pamoate
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus