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Published on: June 9, 2016
Small molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies
1Neurosurgical Center Amsterdam, VU University Medical Center, De Boelelaan 1117, Amsterdam, The Netherlands. p.dewitthamer@vumc.nl
Abstract:
The efficacy of small-molecule kinase inhibitors has recently changed standard clinical practice for several solid cancers. Glioblastoma is a solid cancer that universally recurs and unrelentingly results in death despite maximal surgery and radiotherapy with concomitant and adjuvant temozolomide. Several clinical studies using kinase inhibitors in glioblastoma have been reported. The present study systematically reviews the efficacy, toxicity, and tissue analysis of small-molecule kinase inhibitors in adult patients with glioblastoma as reported in published clinical studies and determines which kinases have been targeted by the inhibitors used in these studies. Publications were retrieved using a MEDLINE search and by screening meeting abstracts. A total of 60 studies qualified for inclusion, of which 25 were original reports. A total of 2385 glioblastoma patients receiving kinase inhibitors could be evaluated. The study designs included 2 phase III studies and 37 phase II studies. Extracted data included radiological response, progression-free survival, overall survival, toxicity, and biomarker analysis. The main findings were that (i) efficacy of small-molecule kinase inhibitors in clinical studies with glioblastoma patients does not yet warrant a change in standard clinical practice and (ii) 6 main kinase targets for inhibitors have been evaluated in these studies: EGFR, mTOR, KDR, FLT1, PKCbeta, and PDGFR.
Insights
Small-molecule kinase inhibitors show limited efficacy in glioblastoma clinical studies, not yet changing standard treatment. Six main kinase targets, including EGFR and mTOR, have been evaluated in this aggressive brain cancer.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Glioblastoma is an aggressive brain cancer with poor prognosis despite standard treatments.
- Small-molecule kinase inhibitors have transformed care in other solid tumors.
- Their role in glioblastoma remains under investigation.
Purpose of the Study:
- To systematically review the efficacy, toxicity, and tissue analysis of small-molecule kinase inhibitors in glioblastoma.
- To identify targeted kinases and assess their clinical impact.
Main Methods:
- Systematic review of published clinical studies retrieved via MEDLINE and conference abstracts.
- Inclusion of 60 studies evaluating 2385 glioblastoma patients.
- Data extraction on radiological response, survival, toxicity, and biomarkers.
Main Results:
- Current clinical studies show small-molecule kinase inhibitors do not warrant changes to standard glioblastoma care.
- Efficacy data is insufficient to alter treatment paradigms.
- Six primary kinase targets were evaluated: EGFR, mTOR, KDR, FLT1, PKCbeta, and PDGFR.
Conclusions:
- Small-molecule kinase inhibitors have not yet demonstrated sufficient efficacy to change standard glioblastoma treatment.
- Further research is needed to identify effective kinase targets and therapeutic strategies for glioblastoma.
