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

J Neurooncol. 2019 May;143(1):107-113. doi: 10.1007/s11060-019-03140-z. Epub 2019 Mar 4.

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/m2 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.

Keywords: Children; DIPG; Diffuse midline glioma; EGFR; Nimotuzumab; Radiotherapy.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Brain Stem Neoplasms / diagnostic imaging
  • Brain Stem Neoplasms / therapy*
  • Chemoradiotherapy* / adverse effects
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Glioma / diagnostic imaging
  • Glioma / therapy*
  • Humans
  • Male
  • Pons
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • nimotuzumab