Systemic management of malignant meningiomas: A comparative survival and molecular marker analysis between Octreotide in combination with Everolimus and Sunitinib

PLoS One. 2019 Jun 20;14(6):e0217340. doi: 10.1371/journal.pone.0217340. eCollection 2019.

Abstract

Purpose: To compare the effectiveness of octreotide/everolimus vs. sunitinib for the systemic treatment of recurrent aggressive meningiomas.

Methods: 31 patients with recurrent or refractory WHO II or WHO III meningiomas were examined in two reference centers in Colombia. Patients who had systemic treatment (sunitinib, everolimus/octreotide) and a complete follow-up were included. Overall survival (OS), progression-free survival (PFS) and toxicities were evaluated. Additionally, tissue samples were examined for PDGFRβ and VEGFR2, their expression was correlated with outcomes.

Results: Twenty-two patients (72%) were female with a median age of 55 years (SD±15.3). The most prevalent histology was anaplastic meningioma in 20 patients (65%) with 48% of patients suffering from three previous relapses before the start of systemic treatment. A total of 14 patients received combination therapy with octreotide/everolimus, 11 received sunitinib and the remaining 6 received other second-line agents. Median OS was 37.3 months (95%CI 28.5-42.1) and the PFS during the treatment with everolimus/octreotide (EO) and sunitinib (Su) was 12.1 months (95%CI 9.2-21.1) and 9.1 months (95%CI 6.8-16.8); p = 0.43), respectively. The OS of the group treated with the EO→Su→Bev sequence (1st/2nd/3rd line) was 6.5 months longer than the Su→EO→Bev sequence (36.0 vs. 29.5 months) (p = 0.0001). When analyzing molecular markers, the positive PDGFRβ and negative VEGFR2 expression were associated with longer survival both in OS and PFS.

Conclusion: Sunitinib and octreotide/everolimus have similar efficacy and safety in the systemic management of refractory meningioma. VEGFR2 and PDGFRβ expression are associated with better outcomes.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Biomarkers, Tumor / blood*
  • Disease-Free Survival
  • Everolimus / administration & dosage
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Meningeal Neoplasms* / blood
  • Meningeal Neoplasms* / drug therapy
  • Meningeal Neoplasms* / mortality
  • Meningioma* / blood
  • Meningioma* / drug therapy
  • Meningioma* / mortality
  • Middle Aged
  • Neoplasm Proteins / blood*
  • Octreotide / administration & dosage
  • Receptor, Platelet-Derived Growth Factor beta / blood*
  • Retrospective Studies
  • Sunitinib / administration & dosage
  • Survival Rate
  • Vascular Endothelial Growth Factor Receptor-2 / blood*

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Everolimus
  • KDR protein, human
  • PDGFRB protein, human
  • Receptor, Platelet-Derived Growth Factor beta
  • Vascular Endothelial Growth Factor Receptor-2
  • Octreotide
  • Sunitinib

Grants and funding

Supported by the Foundation for Clinical and Applied Cancer Research - FICMAC (Bogotá Colombia) research grant 011-2017SD awarded to Andrés F. Cardona. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.