Phase 2 study of safety and efficacy of nimotuzumab in pediatric patients with progressive diffuse intrinsic pontine glioma.

Abstract

BACKGROUND:

The prognosis of diffuse intrinsic pontine glioma (DIPG) remains poor, with no drug proven to be effective.

METHODS:

Patients with clinically and radiologically confirmed, centrally reviewed DIPG, who had failed standard first-line therapy were eligible for this multicenter phase II trial. The anti-epidermal growth factor receptor (EGFR) antibody, nimotuzumab (150 mg/m(2)), was administered intravenously once weekly from weeks 1 to 7 and once every 2 weeks from weeks 8 to 18. Response evaluation was based on clinical and MRI assessments. Patients with partial response (PR) or stable disease (SD) were allowed to continue nimotuzumab.

RESULTS:

Forty-four patients received at least one dose of nimotuzumab (male/female, 20/24; median age, 6.0 years; range, 3.0-17.0 years). All had received prior radiotherapy. Treatment was well tolerated. Eighteen children experienced serious adverse events (SAEs). The majority of SAEs were associated with disease progression. Nineteen patients completed 8 weeks (W8) of treatment: There were 2 PRs, 6 SDs, and 11 progressions. Five patients completed 18 weeks (W18) of treatment: 1 of 2 patients with PR at W8 remained in PR at W18, and 3 of 6 children with SD at W8 maintained SD at W18. Time to progression following initiation of nimotuzumab for the 4 patients with SD or better at W18 was 119, 157, 182 and 335 days, respectively. Median survival time was 3.2 months. Two patients lived 663 and 481 days from the start of nimotuzumab.

CONCLUSIONS:

Modest activity of nimotuzumab in DIPG, which has been shown previously, was confirmed: A small subset of DIPG patients appeared to benefit from anti-EGFR antibody treatment.

• Authors: Ute Bartels, Johannes Wolff, Lia Gore, Ira Dunkel, Stephen Gilheeney, Jeffrey Allen, Stewart Goldman, Michal Yalon, Roger J Packer, David N Korones, Amy Smith, Kenneth Cohen, John Kuttesch, Douglas Strother, Sylvain Baruchel, Janet Gammon, Mark Kowalski, Eric Bouffet
• Journal: Neuro-oncology (Neuro Oncol) Vol. 16 Issue 11 Pg. 1554-9 (Nov 2014) ISSN: 1523-5866 [Electronic] England
• PMID: 24847085 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antibodies, Monoclonal, Humanized
• nimotuzumab

Topics

• Adolescent
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Brain Stem Neoplasms (drug therapy, mortality, pathology)
• Child
• Child, Preschool
• Cohort Studies
• Disease Progression
• Female
• Follow-Up Studies
• Glioma (drug therapy, mortality, pathology)
• Humans
• Male
• Neoplasm Recurrence, Local (drug therapy, mortality, pathology)
• Neoplasm Staging
• Prognosis
• Safety
• Survival Rate