Manfred Westphal1, Oliver Heese2, Joachim P Steinbach3, Oliver Schnell4, Gabriele Schackert5, Maximilian Mehdorn6, Dirk Schulz7, Matthias Simon8, Uwe Schlegel9, Christian Senft10, Karsten Geletneky11, Christian Braun12, Joachim G Hartung13, Dirk Reuter14, Monika Warmuth Metz15, Ferdinand Bach16, Torsten Pietsch17. 1. Department of Neurosurgery, University Hospital Hamburg Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Electronic address: westphal@uke.de. 2. Department of Neurosurgery, University Hospital Hamburg Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Electronic address: oliver.heese@helios-kliniken.de. 3. Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany. Electronic address: joachim.steinbach@med.uni-frankfurt.de. 4. Department of Neurosurgery, Ludwig Maximilian University München-Grosshadern, Marchioninistrasse 15, 81377 München, Germany. Electronic address: oliver.schnell@med.uni-muenchen.de. 5. Department of Neurosurgery, Carus University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Electronic address: gabriele.schackert@uniklinikum-dresden.de. 6. Department of Neurosurgery, Christian Albrecht Universität Kiel, Schittenhelmstrasse 10, 24106 Kiel, Germany. Electronic address: maximilian.mehdorn@uksh.de. 7. Department of Neurosurgery, Justus Liebig University Giessen, Klinikstrasse 33, 35392 Gießen, Germany. Electronic address: dirk.schulz@neuro.med.uni-giessen.de. 8. Department of Neurosurgery, University Hospital Bonn, Sigmund-Freud Strasse 25, 53105 Bonn, Germany. Electronic address: matthias.simon@ukb.uni-bonn.de. 9. Department of Neurology, Ruhr Universität Bochum, In der Schornau 23-25, 44892 Bochum, Germany. Electronic address: uwe.schlegel@kk-bochum.de. 10. Department of Neurosurgery, University Hospital Frankfurt, Schleusenweg 2-16 (Haus 95), 60528 Frankfurt am Main, Germany. Electronic address: c.senft@med.uni-frankfurt.de. 11. Department of Neurosurgery, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Electronic address: karsten.geletneky@med.uni-heidelberg.de. 12. Department of Neurology, University Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany. Electronic address: christian.braun@medizin.uni-tuebingen.de. 13. Universität Dortmund, Fachbereich Statistik, 44221 Dortmund, Germany. Electronic address: jghartung@aol.com. 14. Oncoscience AG, Wedel, Hafenstrasse 32, 22880 Wedel, Germany. Electronic address: d.reuter@oncoscience-ag.de. 15. Department of Neuroradiology, University Hospital Würzburg, Josef-Schneiderstrasse 11, 97080 Würzburg, Germany. Electronic address: warmuth-metz@neuroradiologie.uni-wuerzburg.de. 16. Oncoscience AG, Wedel, Hafenstrasse 32, 22880 Wedel, Germany. Electronic address: f.bach@oncoscience-ag.de. 17. Institute for Neuropathology, University Hospital Bonn, Sigmund-Freud Strasse 25, 53105 Bonn, Germany. Electronic address: t-pietsch@uni-bonn.de.
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 400mg weekly added to standard radiochemotherapy followed by 400mg 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). 12 moPFS 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.
RCT Entities:
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 glioblastomapatients stratified as with or without residual tumour were randomly assigned to receive either intravenous nimotuzumab 400mg weekly added to standard radiochemotherapy followed by 400mg 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). 12 moPFS was 25.6% in the experimental arm and 20.3% in the control group. In residual tumourpatients (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.
Authors: Neha Kamran; Alexandra Calinescu; Marianela Candolfi; Mayuri Chandran; Yohei Mineharu; Antonela S Asad; Carl Koschmann; Felipe J Nunez; Pedro R Lowenstein; Maria G Castro Journal: Expert Opin Biol Ther Date: 2016-07-27 Impact factor: 4.388
Authors: Neha Kamran; Mahmoud S Alghamri; Felipe J Nunez; Diana Shah; Antonela S Asad; Marianela Candolfi; David Altshuler; Pedro R Lowenstein; Maria G Castro Journal: Immunotherapy Date: 2018-02-01 Impact factor: 4.196
Authors: Eskil Eskilsson; Gro V Røsland; Gergely Solecki; Qianghu Wang; Patrick N Harter; Grazia Graziani; Roel G W Verhaak; Frank Winkler; Rolf Bjerkvig; Hrvoje Miletic Journal: Neuro Oncol Date: 2018-05-18 Impact factor: 12.300
Authors: Adrian Lee; Malmaruha Arasaratnam; David Lok Hang Chan; Mustafa Khasraw; Viive M Howell; Helen Wheeler Journal: Cochrane Database Syst Rev Date: 2020-05-12