417O - Mgmt Methylation in Tissue and Serum from Unresectable Glioblastoma (Gbm) Patients (P) Included in the Genom 009 Study, a Multicenter Randomized Study By the Geino Group Comparing Temozolomide (Tmz) Versus Tmz-Plus-Bevacizumab (Bev). (Clinicaltrials.Gov Nct01102595)

Abstract

ABSTRACT Aim: We compared treatment with TMZ versus TMZ + BEV prior to and concomitant with radiotherapy in unresectable GBM p. The potential prognostic role of MGMT methylation was examined in p with available tissue and/or serum samples. Methods: Patients were randomly assigned to receive either TMZ (200 mg/m2, days 1–5, for two 28-day cycles), followed by TMZ with concomitant radiotherapy (60Gy) (TMZ Arm) or the same regimen with the addition of BEV (10mg/kg /15 days) (BEV Arm). Both arms then received adjuvant TMZ for 6 cycles. The primary endpoint was overall response rate (ORR) according to RANO criteria after the two pre-radiotherapy cycles. Secondary endpoints included the analysis of MGMT methylation in serum and/or tissue as a potential prognostic marker. MGMT methylation was analyzed in a blinded fashion in two separate molecular biology laboratories using identical techniques. Results: 93 p were randomized – 45 to the TMZ Arm and 48 to the BEV Arm. ORR was higher in the BEV Arm (P = 0.001). Progression-free survival (PFS), overall survival (OS) and 1-year survival were longer in the BEV Arm but differences did not reach statistical significance. MGMT methylation was analyzed in tissue samples from 60 p, 55 of whom were evaluable for response and survival; MGMT was methylated in 28 and unmethylated in 29 (3 no evaluable). MGMT methylation was analyzed in serum samples from 77 p, 72 of whom were evaluable for response and survival; MGMT was methylated in 11 and unmethylated in 61 p. In 40 p with MGMT methylation results in both tissue and serum, no significant concordance between tissue and serum methylation was observed. Tissue MGMT methylation was associated with longer PFS (P = 0.01), OS (P = 0.001) and 1-year survival (P = 0.004), but no association between serum MGMT methylation and outcome was observed: PFS (P = 0.72). OS (P = 0.84) or 1-year survival (P = 0.98). Conclusions: MGMT methylation in serum is not useful to predict outcome in GBM p. The low proportion of p with serum MGMT methylation suggests a possible contamination of DNA with lymphocytes. Disclosure: C. Balana: Carmen Balana is a membership of advisory boards of Roche and has a grant from Roche and MSD to perform this study. All other authors have declared no conflicts of interest.