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

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

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Purpose/Objective(s) 

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.

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Materials/Methods 

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.

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Results 

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.

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Conclusions 

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.