Title: Is Long-Term Survival in Glioblastoma Possible? Updated Results of the EORTC/NCIC Phase III Randomized Trial on Radiotherapy (RT) and Concomitant and Adjuvant Temozolomide (TMZ) versus RT Alone
Abstract: The addition of concomitant and adjuvant Temozolomide (TMZ) to radiotherapy (RT) improves median and 2-year survival in Glioblastoma (GBM) (Stupp et al, NEJM 2005). However it is not known yet whether this survival advantage will remain with a longer follow-up. We report here the updated results of our phase III trial by the EORTC Brain Tumor Group, the Radiation Oncology Group and the NCIC Clinical Trials Group. Patients aged 18–70 years with newly diagnosed GBM (WHO grade IV), PS (WHO) 0–2, were eligible. They were randomized between standard RT (60 Gy in 30 daily fraction of 2 Gy, with a GTV-CTV margin of 2–3 cm), versus the same RT with concomitant TMZ (75 mg/m2 daily 7 d/wk for 35–42 d), followed by up to 6 cycles of adjuvant TMZ (150–200 mg/m2, daily × 5 d, q 28 d). Primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), quality of life (Taphoorn et al, Lancet Oncology 2005), and toxicity profile. Five hundred and seventy-three patients were randomized between July 2000 and March 2002. Repartition of prognostic categories was: 15%, 52% and 33% for RPA classes III, IV and V, respectively, and was equally distributed in the 2 arms. With a mean follow-up for surviving patients of 45.9 months, the median survival was 12.1 months (95% CI 11.2–13.0) in the RT arm and 14.6 months (95% CI 13.2–16.8) in the TMZ/RT arm (p < .0001). The 2-, 3- and 4-year survivals were 11.2, 4.3 and 3.8% in the RT arm, versus 27.3, 16.7 and 12.9% in the RT/TMZ arm (p < .0001). The impact of RPA class and MGMT gene promoter methylation status remained highly significant on the longer term and will be presented. The survival advantage conferred by the addition of TMZ to RT in GBM remains highly significant with a longer follow-up, and we expect a modest but significant proportion of patients to be long-term survivors, especially those in the RPA III category and those with methylated MGMT.