Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG): a phase III clinical study

G. Fleischhack, M. Massimino, M. Warmuth-Metz, E. Khuhlaeva, G. Janssen, N. Graf, S. Rutkowski, A. Beilken, I. Schmid, V. Biassoni, S. K. Gorelishev, C. Kramm, H. Reinhard, P. G. Schlegel, R. D. Kortmann, D. Reuter, F. Bach, N. E. Iznaga-Escobar, U. Bode

Research output: Contribution to journalArticle

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Abstract

Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating cancer of childhood and adolescence. Methods: The study included patients between 3 and 20 years with clinically and radiologically confirmed DIPG. Primary endpoint was 6-month progression-free survival (PFS) following administration of nimotuzumab in combination with external beam radiotherapy (RT). Nimotuzumab was administered intravenously at 150 mg/m 2 weekly for 12 weeks. Radiotherapy at total dose of 54 Gy was delivered between week 3 and week 9. Response was evaluated based on clinical features and MRI findings according to RECIST criteria at week 12. Thereafter, patients continued to receive nimotuzumab every alternate week until disease progression/unmanageable toxicity. Adverse events (AE) were evaluated according to Common Terminology Criteria for Adverse Events (CTC-AE) Version 3.0 (CTC-AE3). Results: All 42 patients received at least one dose of nimotuzumab in outpatient settings. Two patients had partial response (4.8%), 27 had stable disease (64.3%), 10 had progressive disease (23.8%) and 3 patients (7.1%) could not be evaluated. The objective response rate (ORR) was 4.8%. Median PFS was 5.8 months and median overall survival (OS) was 9.4 months. Most common drug-related AEs were alopecia (14.3%), vomiting, headache and radiation skin injury (7.1% each). Therapy-related serious adverse events (SAEs) were intra-tumoral bleeding and acute respiratory failure, which were difficult to distinguish from effects of tumor progression. Conclusions: Concomitant treatment with RT and nimotuzumab was feasible in an outpatient setting. The PFS and OS were comparable to results achieved with RT and intensive chemotherapy in hospitalized setting.

Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalJournal of Neuro-Oncology
Volume143
Issue number1
DOIs
Publication statusPublished - May 1 2019

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Glioma
Radiotherapy
Disease-Free Survival
Outpatients
Therapeutics
Radiation Injuries
Survival
Alopecia
Terminology
Respiratory Insufficiency
Vomiting
Headache
Disease Progression
Neoplasms
nimotuzumab
Clinical Studies
Hemorrhage
Drug Therapy
Skin
Pharmaceutical Preparations

Keywords

  • Children
  • Diffuse midline glioma
  • DIPG
  • EGFR
  • Nimotuzumab
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG) : a phase III clinical study. / Fleischhack, G.; Massimino, M.; Warmuth-Metz, M.; Khuhlaeva, E.; Janssen, G.; Graf, N.; Rutkowski, S.; Beilken, A.; Schmid, I.; Biassoni, V.; Gorelishev, S. K.; Kramm, C.; Reinhard, H.; Schlegel, P. G.; Kortmann, R. D.; Reuter, D.; Bach, F.; Iznaga-Escobar, N. E.; Bode, U.

In: Journal of Neuro-Oncology, Vol. 143, No. 1, 01.05.2019, p. 107-113.

Research output: Contribution to journalArticle

Fleischhack, G, Massimino, M, Warmuth-Metz, M, Khuhlaeva, E, Janssen, G, Graf, N, Rutkowski, S, Beilken, A, Schmid, I, Biassoni, V, Gorelishev, SK, Kramm, C, Reinhard, H, Schlegel, PG, Kortmann, RD, Reuter, D, Bach, F, Iznaga-Escobar, NE & Bode, U 2019, 'Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG): a phase III clinical study', Journal of Neuro-Oncology, vol. 143, no. 1, pp. 107-113. https://doi.org/10.1007/s11060-019-03140-z
Fleischhack, G. ; Massimino, M. ; Warmuth-Metz, M. ; Khuhlaeva, E. ; Janssen, G. ; Graf, N. ; Rutkowski, S. ; Beilken, A. ; Schmid, I. ; Biassoni, V. ; Gorelishev, S. K. ; Kramm, C. ; Reinhard, H. ; Schlegel, P. G. ; Kortmann, R. D. ; Reuter, D. ; Bach, F. ; Iznaga-Escobar, N. E. ; Bode, U. / Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG) : a phase III clinical study. In: Journal of Neuro-Oncology. 2019 ; Vol. 143, No. 1. pp. 107-113.
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abstract = "Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating cancer of childhood and adolescence. Methods: The study included patients between 3 and 20 years with clinically and radiologically confirmed DIPG. Primary endpoint was 6-month progression-free survival (PFS) following administration of nimotuzumab in combination with external beam radiotherapy (RT). Nimotuzumab was administered intravenously at 150 mg/m 2 weekly for 12 weeks. Radiotherapy at total dose of 54 Gy was delivered between week 3 and week 9. Response was evaluated based on clinical features and MRI findings according to RECIST criteria at week 12. Thereafter, patients continued to receive nimotuzumab every alternate week until disease progression/unmanageable toxicity. Adverse events (AE) were evaluated according to Common Terminology Criteria for Adverse Events (CTC-AE) Version 3.0 (CTC-AE3). Results: All 42 patients received at least one dose of nimotuzumab in outpatient settings. Two patients had partial response (4.8{\%}), 27 had stable disease (64.3{\%}), 10 had progressive disease (23.8{\%}) and 3 patients (7.1{\%}) could not be evaluated. The objective response rate (ORR) was 4.8{\%}. Median PFS was 5.8 months and median overall survival (OS) was 9.4 months. Most common drug-related AEs were alopecia (14.3{\%}), vomiting, headache and radiation skin injury (7.1{\%} each). Therapy-related serious adverse events (SAEs) were intra-tumoral bleeding and acute respiratory failure, which were difficult to distinguish from effects of tumor progression. Conclusions: Concomitant treatment with RT and nimotuzumab was feasible in an outpatient setting. The PFS and OS were comparable to results achieved with RT and intensive chemotherapy in hospitalized setting.",
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T1 - Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG)

T2 - a phase III clinical study

AU - Fleischhack, G.

AU - Massimino, M.

AU - Warmuth-Metz, M.

AU - Khuhlaeva, E.

AU - Janssen, G.

AU - Graf, N.

AU - Rutkowski, S.

AU - Beilken, A.

AU - Schmid, I.

AU - Biassoni, V.

AU - Gorelishev, S. K.

AU - Kramm, C.

AU - Reinhard, H.

AU - Schlegel, P. G.

AU - Kortmann, R. D.

AU - Reuter, D.

AU - Bach, F.

AU - Iznaga-Escobar, N. E.

AU - Bode, U.

PY - 2019/5/1

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N2 - Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating cancer of childhood and adolescence. Methods: The study included patients between 3 and 20 years with clinically and radiologically confirmed DIPG. Primary endpoint was 6-month progression-free survival (PFS) following administration of nimotuzumab in combination with external beam radiotherapy (RT). Nimotuzumab was administered intravenously at 150 mg/m 2 weekly for 12 weeks. Radiotherapy at total dose of 54 Gy was delivered between week 3 and week 9. Response was evaluated based on clinical features and MRI findings according to RECIST criteria at week 12. Thereafter, patients continued to receive nimotuzumab every alternate week until disease progression/unmanageable toxicity. Adverse events (AE) were evaluated according to Common Terminology Criteria for Adverse Events (CTC-AE) Version 3.0 (CTC-AE3). Results: All 42 patients received at least one dose of nimotuzumab in outpatient settings. Two patients had partial response (4.8%), 27 had stable disease (64.3%), 10 had progressive disease (23.8%) and 3 patients (7.1%) could not be evaluated. The objective response rate (ORR) was 4.8%. Median PFS was 5.8 months and median overall survival (OS) was 9.4 months. Most common drug-related AEs were alopecia (14.3%), vomiting, headache and radiation skin injury (7.1% each). Therapy-related serious adverse events (SAEs) were intra-tumoral bleeding and acute respiratory failure, which were difficult to distinguish from effects of tumor progression. Conclusions: Concomitant treatment with RT and nimotuzumab was feasible in an outpatient setting. The PFS and OS were comparable to results achieved with RT and intensive chemotherapy in hospitalized setting.

AB - Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating cancer of childhood and adolescence. Methods: The study included patients between 3 and 20 years with clinically and radiologically confirmed DIPG. Primary endpoint was 6-month progression-free survival (PFS) following administration of nimotuzumab in combination with external beam radiotherapy (RT). Nimotuzumab was administered intravenously at 150 mg/m 2 weekly for 12 weeks. Radiotherapy at total dose of 54 Gy was delivered between week 3 and week 9. Response was evaluated based on clinical features and MRI findings according to RECIST criteria at week 12. Thereafter, patients continued to receive nimotuzumab every alternate week until disease progression/unmanageable toxicity. Adverse events (AE) were evaluated according to Common Terminology Criteria for Adverse Events (CTC-AE) Version 3.0 (CTC-AE3). Results: All 42 patients received at least one dose of nimotuzumab in outpatient settings. Two patients had partial response (4.8%), 27 had stable disease (64.3%), 10 had progressive disease (23.8%) and 3 patients (7.1%) could not be evaluated. The objective response rate (ORR) was 4.8%. Median PFS was 5.8 months and median overall survival (OS) was 9.4 months. Most common drug-related AEs were alopecia (14.3%), vomiting, headache and radiation skin injury (7.1% each). Therapy-related serious adverse events (SAEs) were intra-tumoral bleeding and acute respiratory failure, which were difficult to distinguish from effects of tumor progression. Conclusions: Concomitant treatment with RT and nimotuzumab was feasible in an outpatient setting. The PFS and OS were comparable to results achieved with RT and intensive chemotherapy in hospitalized setting.

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