Abstract
Purpose
The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data.
Methods
GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data.
Results
205 patients were recruited: 159 in GEINO14-01 (2014–2018) and 46 in EX-TEM (2019–2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation.
Conclusion
For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.
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Data availability
The data generated in this study are not publicly available as this would compromise patient consent, but are available upon reasonable request from the corresponding author.
Change history
30 January 2024
A Correction to this paper has been published: https://doi.org/10.1007/s11060-024-04581-x
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Funding
The studies were supported financially by the Victoria Comprehensive Cancer Centre (EX-TEM) and a grant from the Spanish Institute Carlos III (ISCIII: PI13/01751 to Carmen Balana) (GEINO14-01). Analysis and manuscript preparation was made possible in part through the authors’ membership of the Brain Cancer Centre.
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L.G., M.R., P.G, and C.B. contributed to the study conception and design. Material preparation and data collection was performed by all authors. Analysis was performed by L.G. and W.H. The first draft of the manuscript was written by L.G. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Gately, L., Mesía, C., Sepúlveda, J.M. et al. A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma. J Neurooncol 166, 407–415 (2024). https://doi.org/10.1007/s11060-023-04513-1
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DOI: https://doi.org/10.1007/s11060-023-04513-1