Predictive role of MGMT status in recurrent glioblastoma (GBM) patients (PTS) treated with antiangiogenic drug (AD) plus temozolomide (TMZ) or CPT-11.

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2049 Background: Methylation and silencing of MGMT promoter is a favourable predictive factor in PTS with GBM treated with single alkylating agent such as TMZ. Yet, MGMT is an important resistance determinant to CPT-11 activity. AD can be administered in second line treatment as single agent or in combination to cytotoxic drugs. We analyzed the predictive role of MGMT status in PTS treated with AD plus TMZ or CPT-11 as second line treatment. Methods: Retrospectively, 55 PTS were analyzed: 36 (65%) with unmethlyated MGMT, 19 (35%) with methylated MGMT; 3 (5%) PTS with IDH1 mutations. 17 (31%) PTS performed a reoperation before the second line treatment and MGMT status was changed in 2 (18%) PTS, IDH1 status was unchanged in all PTS. 32 PTS were treated with sorafenib 800mg/die plus TMZ 40mg/m2/die, 23 with bevacizumab 10mg/Kg plus irinotecan every two weeks. Tumor response was evaluated by clinician assessment and by MRI according to RANO criteria every two months or when clinically indicated. Results: Among all PTS, median PFS was 2.7 months (95%CI 1.5-3.5), median OS from start of AD was 7.3 months (95%CI 6.02-8.5), 6-month PFS was 32%; no significant differences were observed and MGMT status was balanced between the two AD groups (p>0.05). Analyzing MGMT status at first surgery, according to univariate analyses there were no significant differences in terms of PFS (3.5ms vs 2.1ms; p=0.2), OS (6.5ms vs 7.2ms; p=0.1) and 6-PFS (HR=0.2, CI95% 0.05-1.07) between PTS with unmethylated and methylated MGMT, respectively. On multivariate analysis, adjusted for performance status, age and cytotoxic drug, MGMT status was not statistically significant in terms of PFS (p=0.8) and OS (p=0.1). Yet, no significant differences emerged with MGMT status at second surgery as well as analyzing the two AD groups, separately. Conclusions: MGMT status might not be a predictive factor in recurrent GBM patients treated with AD plus TMZ or CPT-11 as second line treatment, although MGMT status may change in some PTS between first and second surgery. In conclusion, the outcome of patients with recurrent GBM receiving AD plus TMZ or CPT-11 is not significantly influenced by MGMT methylation status.