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Published on: July 16, 2018
Optimized Image-Based Surrogate Endpoints in Targeted Therapies for Glioblastoma: A Systematic Review and
Chong Hyun Suh1, Ho Sung Kim2, Seung Chai Jung1
1Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Objective:
We aimed to determine the optimized image-based surrogate endpoints (IBSEs) in targeted therapies for glioblastoma through a systematic review and meta-analysis of phase III randomized controlled trials (RCTs).
Materials And Methods:
A systematic search of OVID-MEDLINE and EMBASE for phase III RCTs on glioblastoma was performed in December 2017. Data on overall survival (OS) and IBSEs, including progression-free survival (PFS), 6-month PFS (6moPFS), 12-month PFS (12moPFS), median PFS, and objective response rate (ORR) were extracted. Weighted linear regression analysis for the hazard ratio for OS and the hazard ratios or odds ratios for IBSEs was performed. The associations between IBSEs and OS were evaluated. Subgroup analyses according to disease stage (newly diagnosed glioblastoma versus recurrent glioblastoma), types of test treatment, and types of response assessment criteria were performed.
Results:
Twenty-three phase III RCTs published between 2000 and 2017, including 8387 patients, met the inclusion criteria. OS showed strong correlations with PFS (standardized β coefficient [R] = 0.719), 6moPFS (R = 0.647), and 12moPFS (R = 0.638). OS showed no correlations with median PFS and ORR. In subgroup analysis according to types of therapies, PFS showed the highest correlations with OS in targeted therapies for cell cycle pathways (R = 0.913) and growth factor receptors and their downstream pathways (R = 0.962). 12moPFS showed the highest correlation with OS in antiangiogenic therapy (R = 0.821). The response assessment in neuro-oncology criteria provided higher correlation coefficients between OS and IBSEs than the Macdonald criteria.
Conclusion:
Overall, PFS is an optimized IBSE in targeted therapies for glioblastoma; however, 12moPFS is optimal in antiangiogenic therapy.
Insights
Progression-free survival (PFS) is an optimized image-based surrogate endpoint for glioblastoma targeted therapies. However, 12-month PFS is most effective for antiangiogenic therapies, showing strong correlation with overall survival.
Area of Science:
- Neuro-oncology
- Clinical Trials
- Biostatistics
Background:
- Glioblastoma treatment relies on targeted therapies, necessitating validated surrogate endpoints for clinical trials.
- Image-based surrogate endpoints (IBSEs) are crucial for assessing treatment efficacy in glioblastoma.
- Optimizing IBSEs can accelerate drug development and improve patient outcomes.
Purpose of the Study:
- To systematically review and meta-analyze phase III randomized controlled trials (RCTs) to identify optimized IBSEs for glioblastoma targeted therapies.
- To evaluate the correlation between various IBSEs and overall survival (OS) in glioblastoma patients.
Main Methods:
- Systematic search of OVID-MEDLINE and EMBASE for phase III RCTs on glioblastoma (published 2000-2017).
- Extracted data on OS and IBSEs (PFS, 6moPFS, 12moPFS, median PFS, ORR).
- Weighted linear regression and subgroup analyses were performed to assess associations between IBSEs and OS.
Main Results:
- Twenty-three RCTs (8387 patients) were included. PFS, 6-month PFS, and 12-month PFS showed strong correlations with OS.
- PFS demonstrated the highest correlation with OS in targeted therapies for cell cycle and growth factor pathways.
- 12-month PFS showed the strongest correlation with OS in antiangiogenic therapy.
Conclusions:
- Progression-free survival (PFS) is an optimized IBSE for glioblastoma targeted therapies.
- 12-month PFS is the optimal IBSE for antiangiogenic glioblastoma therapy.
- Response assessment criteria influence the correlation strength between IBSEs and OS.
