Are we providing best-available care to newly diagnosed glioblastoma patients? Systematic review of phase III trials in newly diagnosed glioblastoma 2005-2022.

Background: Glioblastoma is the most aggressive primary brain cancer with a poor prognosis. Despite numerous studies in the past 17 years, effective treatment options for glioblastoma remain limited. In this study, we aimed to identify and compare phase III clinical trials for glioblastoma in terms of efficacy and baseline characteristics.
Methods: A systematic literature search was conducted using PubMed and ClinicalTrials.gov to identify phase III clinical trials for glioblastoma in adult patients. The target population included adult patients aged 18 years and above (younger cohort) and patients ≥60 years of age (elderly cohort). The search results were screened based on predefined inclusion criteria, and the included trials were analyzed for their study design, baseline characteristics, and survival results.
Results: Eleven trials met the inclusion criteria in the younger cohort. Of these, three reported a statistically significant improvement in overall survival (OS), including the EORTC/NCIC study (NCT00006353), EF-14 (NCT00916409), and CeTeG (NCT01149109). Of the 11 trials, eight were open-label randomized trials, including all of the positive ones, while three negative trials employed treatment blinding and a placebo control. The baseline characteristics of the trials [such as extent of resection, age, gender, and O (6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status] did not significantly differ between positive and negative trials. Isocitrate dehydrogenase (IDH) mutation status was analyzed in only two trials, with a small percentage of IDH-mutated tumors in each. Additionally, three more trials in the elderly cohort showed a statistically significant improvement of OS, the NOA-08 trial, the ISRCTN81470623-trial by Malmström et al. and NCT00482677-trial by Perry et al. Their baseline characteristics and implications are also analyzed.
Conclusion: This analysis of phase III clinical trials for glioblastoma conducted since 2005 showed that the majority of trials did not result in a significant improvement in OS. Among the trials included in this analysis, only the EORTC/NCIC, EF-14, and CeTeG studies demonstrated a positive OS outcome in the younger cohort.
Competing Interests: Christoph Oster received honoraria from Horizon. He also received travel support from Novocure. Lazaros Lazaridis, and Teresa Schmidt received honoraria and travel support from Novocure. Martin Glas has received research grant from Novocure. He has received honoraria from Roche, Seagan, Servier, Novartis, UCB, Abbvie, Daiichi Sankyo, Bayer, Janssen-Cilag, Kyowa Kirin, Medac, Merck and Novocure. He has received travel support from Novocure and Medac. Sied Kebir has Consulting/advisory role to Novocure. He has received travel support from Merck and Novocure. He got honoraria from Biogen, Merck and Novocure. Björn Scheffler is supported by the German Cancer Consortium (DKTK) and the DFG-CRU337. Christoph Kleinschnitz, Sarina Agkatsev and Ulrich Sure declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)