417O - MGMT methylation in tissue and serum from unresectable glioblastoma (GBM) patients (p) included in the GENOM 009 study, a multicenter randomized st...

Date 27 September 2014
Event ESMO 2014
Session CNS tumours
Topics Anti-Cancer Agents & Biologic Therapy
Central Nervous System Malignancies
Personalised Medicine
Presenter Carmen Balana
Citation Annals of Oncology (2014) 25 (suppl_4): iv137-iv145. 10.1093/annonc/mdu330
Authors C. Balana1, C. Sanz2, J.L. Ramirez1, J.M. Gil3, J.M. Sepúlveda4, R. De Las Penas5, R. Luque6, O. Gallego7, G. Reynes8, C. Carrato9, B. Sanchez1, A. Herrero10, A. Berrocal11, P. Perez Segura12, A. Garcia Castano13, S. Peralta14, S. Vazquez15, I. Fernandez Perez16, M. Martinez-Garcia17
  • 1Medical Oncology, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, 08916 - Badalona(Barcelona)/ES
  • 2Pathology, Hospital Germans Trias i Pujol, Badalona Barcelona/ES
  • 3Medical Oncology, Catalan Institute of Oncology, 08907 - L´Hospitalet (Barcelona)/ES
  • 4Medical Oncology, University Hospital 12 de Octubre, 28041 - Madrid/ES
  • 5Medical Oncology, Hospital Provincial de Castellon, Castellon/ES
  • 6Medical Oncology Unit, Hospital Universitario Virgen de las Nieves, 18014 - Granada/ES
  • 7Medical Oncology, Hospital Sant Pau, Barcelona/ES
  • 8Medical Oncology, Hospital Universitari i Politècnic La Fe, Valencia/ES
  • 9Pathology, Hospital Germans Trias i Pujol, Badalona( Barcelona)/ES
  • 10Medical Oncology, Hospital Miquel Servet, Zaragoza/ES
  • 11Medical Oncology, Hospital General Universitario Valencia, 46014 - Valencia/ES
  • 12Medical Oncology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 13Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander/ES
  • 14Medical Oncology, Hospital Sant Joan de Reus, Tarragona/ES
  • 15Medical Oncology, Hospital Universitario Lucus Augusti de Lugo, Lugo/ES
  • 16Medical Oncology, Hospital Xeral Cies Vigo, Vigo/ES
  • 17Medical Oncology, Hospital del Mar, 08003 - Barcelona/ES

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.