Phase II trial of dacomitinib, a pan-HER (human epidermal growth factor receptor) tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification

Abstract

Background.

We conducted a multicenter, 2-stage, open-label, phase II trial to assess the efficacy and safety of dacomitinib in adult patients with recurrent glioblastoma (GB) and epidermal growth factor receptor (EGFR) gene amplification with or without EGFRvIII deletion.

Methods.

Patients with first recurrence were enrolled in two cohorts: Cohort A) patients with EGFR gene amplification without EGFRvIII mutation; Cohort B) patients with EGFR gene amplification and EGFRvIII mutation. Dacomitinib was administered (45mg/day) until disease progression/unacceptable adverse events (AEs). Primary endpoint was progression-free survival (PFS) [RANO criteria] at 6 months (PFS6).

Results.

30 patients in Cohort A and 19 in Cohort B were enrolled. Median age was 59 years (range 39–81), 65.3% male, ECOG-PS 0/1/2 (10.2%/65.3%/24.5%). PFS6 was 10.6% (Cohort A: 13.3%; Cohort B: 5.9%) with a median PFS of 2.7 months (Cohort A: 2.7 months; Cohort B: 2.6 months). Four patients were progression-free at 6 months and three patients did so at 12 months. Median overall survival was 7.4 months (Cohort A: 7.8 months; Cohort B: 6.7 months). The best overall response included one complete response and two partial responses (4.1%). Stable disease was observed in 12 patients (24.5%: eight Cohort A and four in Cohort B). Diarrhea and rash were the most common AEs; 20 (40.8%) patients experienced grade 3–4 drug-related AEs.

Conclusion.

Dacomitinib has a limited single-agent activity in recurrent GB with EGFR amplification. The detailed molecular characterization of the 4 patients with response in this trial can be useful to select patients that could benefit from dacomitinib.

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