Systemic management of malignant meningioma: A comparative survival and molecular marker analysis between ocreotide in combination with everolimus compared to sunitinib

Abstract

Background: Anaplastic and atypical recurrent meningioma constitute a rare pathology with very few available effective systemic treatments. Methods: A comprehensive analysis of 31 patients with atypical (WHO II) or anaplastic meningiomas (WHO III) that were recurrent and refractory to radiotherapy was conducted in two reference centers of Colombia. Only patients who had received some systemic treatment (sunitinib, everolimus/octeotride and bevacizumab) and had a complete follow‐up were included. Overall survival (OS), progression free survival and toxicities were evaluated. Additionally, tissue samples were examined for PDGFRa and VEGFR2 and its expression was correlated with outcomes. Results: Twenty two patients (72%) were females with a median age of 55 years (SD615.3). 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 octeotride/ everolimus, 11 received sunitinib and the remaining 6 other second line agents. Median OS was 37.3 months (95%CI 28.5‐42.1) and the PFS during the treatment with everolimus/octeotride (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, a finding that was not significant (36.0 vs. 29.5 months; p=0.349). When analyzing molecular markers, the positive PDGFRa and negative VEGFR2 expression were associated with longer survival both in OS and PFS. Conclusions: Sunitinib and ocreotide/everolimus have similar efficacy and safety in the systemic management of refractory meningioma. VEGFR2 and PDGFRa expression are strongly associated with major survival endpoints.