Abstract
Purpose
A randomised, open label phase III trial was conducted to evaluate efficacy of nimotuzumab,
a monoclonal antibody against epidermal growth factor receptor (EGF-R) added to standard
therapy for newly diagnosed glioblastoma.
Patients and methods
149 glioblastoma patients stratified as with or without residual tumour were randomly
assigned to receive either intravenous nimotuzumab 400 mg weekly added to standard radiochemotherapy followed by 400 mg biweekly after twelve weeks or standard radiochemotherapy. Progression status after
52 weeks (12moPFS) and progression-free survival (PFS) based on Macdonald criteria were
co-primary and overall survival (OS), toxicity and quality of life secondary end-points.
Results
142 patients were evaluated for efficacy (per protocol cohort). 12moPFS was 25.6%
in the experimental arm and 20.3% in the control group. In residual tumour patients
(n = 81) median PFS was 5.6 versus 4.0 months, (hazard ratio (HR), 0.87; 95% confidence interval (CI), 0.55–1.37), for patients
without residual tumour (n = 61) it was 10.6 versus 9.9 months, (HR, 1.01; 95% CI, 0.57–1.77). Median OS in patients with residual tumour
was 19.5 versus 16.7 months, (HR, 0.90; 95% CI, 0.52–1.57; P = 0.7061), for patients without 23.3 versus 21.0 months (HR, 0.77; 95% CI, 0.41–1.44; P = 0.4068). A small cohort of MGMT non-methylated patients with residual tumour showed PFS of 6.2 versus 4.0 months (HR, 0.77; 95% CI, 0.35–1.67; P = 0.4997) and OS of 19.0 versus 13.8 months (HR, 0.66; 95% CI, 0.27–1.64; P = 0.3648). EGF-R amplification did not correlate with clinical efficacy of nimotuzumab.
Nimotuzumab was well tolerated.
Conclusion
This study, albeit negative, contains hypothesis generating signals supporting evaluation
of correlative, efficacy-predicting tumour parameters for nimotuzumab in the treatment
of glioblastoma.
Keywords
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Article info
Publication history
Published online: January 20, 2015
Accepted:
December 20,
2014
Received in revised form:
December 11,
2014
Received:
September 23,
2014
Footnotes
☆The study was sponsored by OncoScience AG, Wedel, Germany.
Identification
Copyright
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
