Abstract CT187: Comparative analysis of randomized glioblastoma Phase III trials since 2005
Authors: Lazaridis Lazaros , Stoppek Ann-Kathrin , Schmidt Teresa , Glas Martin , Kebir Sied 
Published: August 2019

Abstract
Objective: We aimed to identify and compare glioblastoma (GBM) Phase III trials of the years 2005 to 2018.
Methods:A systematic literature search using PubMed and ClinicalTrials.gov was conducted to provide an overview of clinically relevant GBM Phase III trials (years 2005-2018) that also included younger adult patients. A comparative analysis of positive and negative trails as well as a detailed overview of the main findings of the trials with demonstrated significantly improved survival will be shown.
Results: Searching PubMed.gov for “glioblastoma OR gbm” and filtering for Phase III clinical trials identified 61 publications. A query on ClinicalTrials.gov for “glioblastoma” filtering for “completed, terminated, interventional, adult, older adult, Phase III” found 29 entries. Among these trials a total of three GBM Phase III trials reporting OS benefit, including the EORTC/NCIC study (PMID: 15758009), EF-14 (NCT00916409) and CeTeG (NCT01149109). A broad overview of the studies identified and a comparison between negative and positive trials will be provided. The latest two identified trials (EF-14 and CeTeG) will be described in more detail. The EF-14 trial randomized 695 patients with newly diagnosed GBM, irrespective of MGMT promoter methylation status, to treatment with temozolomide (TMZ) or tumor treating fields (TTFields) plus TMZ (TTFields/TMZ). ITT analysis showed significantly improved OS (p &lt; 0.001), PFS (p &lt; 0.001) and long-term survival rates by the addition of TTFields to TMZ. Pre-specified subgroup analysis showed, the OS benefit independent of canonical prognostic factors, such as KPS, age, MGMT, and extent of resection. Notably, TTFields/TMZ also improved OS in RPA groups III and IV. In the CeTeG trial, 141 patients with GBM and with MGMT promoter methylation only, were randomized to either lomustine (CCNU) plus temozolomide (CCNU/TMZ) or TMZ alone. Results were provided based on a pre-specified modified ITT analysis stratified for center and RPA class. This trial demonstrated a significant improved median OS (p = 0.049) whereas PFS was not improved in comparison to the control group. The combination of TTFields and TMZ was not associated with a significant increase in systemic adverse events (48% vs 44%, P = 0.58; Grade 3-4, ≥ 5% incidence). 52% of patients experienced mild to moderate skin irritation. The combination of CCNU with TMZ led to a moderate increased rate of patients with AEs grade 3/4 compared to TMZ alone. TTFields/TMZ did not negatively influence Quality of life (QoL) except for itchy skin. CCNU/TMZ did not lead to a reduction of QoL or KPS, neither.
Conclusion: This analysis on GBM Phase III trials conducted since 2005 showed that majority of trials did not show a significant improvement in overall survival. CeTeG and EF-14 are, besides trials on elderly patients only, two recent studies with positive survival outcome.
Citation Format: Lazaros Lazaridis, Ann-Kathrin Stoppek, Teresa Schmidt, Martin Glas, Sied Kebir. Comparative analysis of randomized glioblastoma Phase III trials since 2005 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT187.