Eighteen children experienced serious adverse events (SAEs). 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 Rabbit polyclonal to PIWIL3 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 Nazartinib S-enantiomer 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. = 17; 38.7%), etoposide (= 13; 29%), cisplatin (= 8; 18.2%), and vincristine (= 7; 15.9%). Four participants (9.1%) had received bevacizumab as part of their first-line treatment. Thirty-five participants (79.5%) were receiving dexamethasone at the time of study enrollment. Table?1. Patient characteristics = 5), decreased (= 5), increased (= 2), and unknown (= 1). Mean changes in performance status (increases and decreases) from baseline were noted and fluctuated over the course of the study. No clinically meaningful changes were documented. Survival Median time to progression was 1.7 months (95% CI, 1.4C1.9 months) with a range of 0.2C11.0 Nazartinib S-enantiomer months. Median survival time for the entire cohort was 3.2 months (95% CI, 2.2C4.3 months) with a range 0.2C21.8 months (Figs ?(Figs11 and ?and22). Open in a separate windows Fig.?1. Progression-free survival distribution. Open in a separate windows Fig.?2. Overall survival. The mean overall survival of participants who completed induction therapy and showed progressive disease after completion of induction therapy (= 11) was 146 days (range, 87C268 days), which did not differ significantly compared with the overall survival of 282 days (range, 85C663 days) in participants with SD/PR (= 8) (= .06). Discussion The epidermal growth factor receptor (EGFR) has been implicated in the development of high-grade astrocytic tumors. In the adult populace, more than 40% of glioblastomas harbor EGFR amplification, mutation, or overexpression.14 By contrast, EGFR amplification is uncommon in pediatric high-grade gliomas and DIPGs, although EGFR overexpression is often detected without gene amplification. 15 In a study performed on postmortem tissue, Zarghooni et al described EGFR immunopositivity in 7 of 11 (64%) DIPGs and copy number gain in one.16 The UK and French group conducted a trial of the EGFR inhibitor erlotinib in children with DIPG and recurrent high-grade gliomas. In that trial, tissue collection was mandated for inclusion. Overexpression of EGFR (assessed by immunohistochemistry) was found in 8 of 20 (40%) brainstem tumors and 6 of 8 (75%) supratentorial lesions.17 Since EGFR overexpression or level of activity has been associated with responsiveness to EGFR inhibitors in sound tumors, in particular lung cancer, the use of EGFR inhibitors has raised significant hope for the management of high-grade gliomas.14 The primary aim of this phase II study of nimotuzumab was to confirm early data from Fleischhack et al, who reported promising responses in pediatric patients with recurrent high-grade gliomas and DIPG.13 In that trial, 20 children with recurrent DIPG and high-grade glioma were treated with a weekly IV infusion of 150 mg/m2 nimotuzumab for 6 weeks. Those who Nazartinib S-enantiomer did not show evidence of progression were eligible for a consolidation phase consisting of 4 150 mg/m2 infusions Nazartinib S-enantiomer given at a 3-week interval. Six of 17 eligible participants exhibited partial response or stable disease at the end of the 6-week induction phase, including 4 with recurrent DIPG. The authors subsequently updated these results and reported 1 partial response and 9 SD at the end of the 8-week induction period in a group of 21 participants with recurrent DIPG. At week 21, they described 3 partial responses including a sustained response in a participant who received the drug for 14.5 months.13 Our results confirm these results: we observed 2 partial.