The O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide.

Background: There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the O ⁶ -methylguanine-DNA methyltransferase ( MGMT ) promoter methylation on response and progression-free survival (PFS) following initiation of irinotecan and temozolomide (IT), PFS following initiation of vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE), and overall survival (OS).
Materials and Methods: Data of advanced ES patients, treated with IT were retrospectively collected. Patients were required to have progression after prior VDC-IE. MGMT promoter methylation was assessed on non-decalcified Formalin-fixed paraffin embedded (FFPE) tissue using methylation sensitive restriction enzyme-quantitative PCR (MSRE-qPCR). Survival was estimated by the Kaplan-Meier method.
Results: A total of 20 ES patients underwent MGMT promoter methylation testing, and were eligible for analysis. Five patients (25%) had methylated MGMT , whereas the remaining (15; 75%) had unmethylated promoter. Five (25%) had objective response to IT, with no observed difference by promoter methylation (p = 0.76). Median PFS from initiation of IT for methylated vs . unmethylated MGMT patients was 4.9 and 1.2 months, respectively, p = 0.69. Median PFS from date of initiation of VDC-IE was significantly superior in the methylated group; 27.8 vs . 8.6 months, p = 0.034. Median OS was superior but not statistically significant in the methylated group.
Conclusion: MGMT -promoter methylation did not correlate with clinical activity or outcomes following the IT regimen for advanced ES. However, methylated MGMT predicted significantly superior PFS following initiation of the standard VDC-IE protocol.
Competing Interests: Conflict of interest None to declare.
(© 2022 Greater Poland Cancer Centre.)