OS07.5.A Report from the pooled analysis of the randomized trials NORDIC, NOA-8 and CE.6 on elderly patients with glioblastoma

Abstract

Abstract Background The majority of patients diagnosed with glioblastoma are over 60 years old. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for these patients. Two, the NORDIC and NOA-08 (N&N) compared RT versus TMZ head-to-head, the third, CE.6, randomized between hypofractionated RT and the combination of RT+TMZ. All showed significant benefit for the TMZ arms, especially for patients with MGMT promoter methylated tumors. An ongoing pooled analysis of these three trials focuses on identifying significant baseline prognostic factors and assess their value for predicting outcome in relation to treatment. The aim is improved selection of elderly patients with glioblastoma for their optimal treament; RT alone, TMZ with or without concomitant RT or palliative care. Methods The data of two phase 3 studies (N&N) were pooled to build a large dataset and findings are compared to CE.6 trial data. A re-assessment of the clinically most relevant MGMT cut-off is performed. The prognostic value of baseline clinical factors and quality of life scores, determined by the EORTC QLQ-30 and BN-20 questionnaires, are investigated. Data is also analysed to account for a possible impact of sex. Results The N&N dataset includes 715 and the comparative dataset (CE.6) 562 patients. Median age for N&N is 71 years and 73 for CE.6. In N&N and CE.6 respectively, 66.2% versus 70.5% underwent resection and 50.9% and 75.3% were on steroids at the time of study inclusion. In N&N, 401 patients received RT alone and 281 in CE.6, while 314 were randomized to TMZ alone in N&N and 281 to concomitant RT and TMZ in CE.6. For N&N MGMT promoter methylation status was successfully determined for 412 (57.6%) and 354 (63.0%) for CE.6. In a first report, patients with the combination of the comorbidities hypertension, diabetes and/or cerebrovascular insult had poorer prognosis when treated with TMZ. Conclusion An ongoing pooled analysis of the trials NORDIC, NOA-08 and CE.6 is expected to identify factors that will improve personalized medicine for elderly patients with glioblastoma. Reanalyzed MGMT promoter methylation data and the role of baseline quality of life for outcome will be reported.