Extending temozolomide longer than six cycles in glioblastoma: Results of the randomized GEINO-014 trial

Abstract

Abstract Background Standard treatment of glioblastoma (GBM) is focal radiation with concomitant and adjuvant temozolomide (TMZ) for 6 cycles. The GEINO-14-01 trial (NCT02209948) investigated the role of extending adjuvant TMZ to 12 cycles in a randomized multicenter study. Methods Between Aug/2014 and Nov/2018, 166 patients (p) were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment to 12 cycles after proving lack of progression of the disease in the MRI performed before inclusion. The trial was stratified by MGMT status and presence or absence of residual disease (defined as a residual enhancement larger than 1cm on the MRI). The primary endpoint was differences in 6monthsPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors. Results Median age was 60.4 (range 29-83), all p had ECOG≤1 and 86.2% were without DXM treatment. MGMT status: Met: 97 (61%) UnMet:62 (39%). RD yes: 83 (52.2%) and no: 76 (47.8%). At the time of the abstract report 3 patients are still on treatment or control without a documented progression and 5 patients have not been yet 6m in the study: 31 patients (19.5) are still free of progression and 60 patients (37.7%) are still alive. Median (m) PFS has been reached: 7.9 months (95%CI: 6.1-9.8) as well as mOS: 20.9 (95%CI: 17.6-24.1). A methylated status was a factor of better PFS (HR=0.29, 95% CI 0.46-0.95; p=0.029) and better OS (HR=0.43: 95% CI 0.28-0.66; p=0.000) as well as the absence of residual disease (PFS: HR=0.84: 95% CI=0.71-1.01; p=0.068; OS: HR=0.77, 95%CI 0.63-0.96; p=0.019). We didn t find any difference in PFS (HR=1.02, 95%CI 0.85-1.21; p=0.82), or OS (HR=0.90; 0.73-1.11; p=0.34) on extending treatment with temozolomide longer than 6 cycles. Toxicity data and final results are expected for the congress. Conclusions There is no benefit of continuing TMZ treatment for more than 6 cycles in the adjuvant treatment of glioblastoma. Met status and absence of RD are factors of better SLP after adjuvant treatment. Supported by a Grant of the ISCIII: PI13/01751. Clinical trial identification NCT02209948. Legal entity responsible for the study GEINO (Grupo Espanol de Investigacion en Neurooncologia). Funding Supported by a Grant of the ISCIII. Disclosure M.A.V. Salgado: Advisory / Consultancy: Lilly; Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: pharmamar; Advisory / Consultancy: eisai; Advisory / Consultancy: Celgene. All other authors have declared no conflicts of interest.