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Review
. 2024 Jan 22;6(1):vdad174.
doi: 10.1093/noajnl/vdad174. eCollection 2024 Jan-Dec.

Reassessing the efficacy of bevacizumab in newly diagnosed glioblastoma: A systematic review and external pseudodata-based analysis

Giacomo Sferruzza  1   2 , Massimo Malcangi  1   2 , Luca Bosco  1   2   3 , Gaetano Finocchiaro  2
Affiliations
Review

Reassessing the efficacy of bevacizumab in newly diagnosed glioblastoma: A systematic review and external pseudodata-based analysis

Giacomo Sferruzza et al. Neurooncol Adv. .

Abstract

Background: First-line use of bevacizumab for glioblastoma (GBM) was evaluated in 2 phase 3 randomized controlled trials (RCT), demonstrating an impact on progression-free survival but not overall survival (OS). However, the crossover events of these trials raised concerns regarding the reliability of this latter analysis. In this study, we conducted an external control-based reassessment of the bevacizumab efficacy in newly diagnosed GBM (ndGBM) against the standard Stupp protocol.

Methods: A systematic review of the literature was conducted to identify the phase 3 RCTs in ndGBM incorporating the Stupp protocol as an arm. For the selected studies, we extracted individual patient survival pseudodata of the Stupp protocol arm by digitizing the Kaplan-Meier plots. A comprehensive pipeline was established to select suitable control studies as external benchmarks.

Results: Among the 13 identified studies identified in our systematic review, 4 studies resulted as comparable with the AVAglio trial and 2 with the RTOG 0825. Pooled individual patient pseudodata analysis showed no differences in terms of OS when bevacizumab was added to the Stupp protocol.

Conclusions: The external-controlled-based reassessment of the bevacizumab treatment in ndGBM confirmed its lack of efficacy in extending OS. Our study includes a summary table of individual patient survival pseudodata from all phase 3 RCTs in ndGBM employing the Stupp protocol and provides a pipeline that offers comprehensive guidance for conducting external control-based assessments in ndGBM.

Keywords: Kaplan–Meier digitalization; bevacizumab; external controls; newly diagnosed glioblastoma.

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Conflict of interest statement

To the best of our knowledge, none of the authors have conflicts of interest related to the findings or materials presented in this study.

Figures

Figure 1.
Figure 1.
Flowchart of systematic search and study selection, adapted from PRISMA flow diagram. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses, GBM = glioblastoma, ndGBM = newly diagnosed glioblastoma.
Figure 2.
Figure 2.
Overall survival of patients treated with bevacizumab compared to matched external controls. The bevacizumab (dashed line) arms of the AVAglio (a) and RTOG 0825 (b) trials were compared to the Stupp protocol arms (solid line) of the trials, which were selected as external controls based on their clinical and demographic characteristics. Median survival times are indicated by the black dotted lines, and the 95% CI is depicted in the shaded area.
See this image and copyright information in PMC

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