RT Journal Article
T1 Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification.
A1 Sepulveda-Sanchez, Juan Manuel
A1 Vaz, Maria Angeles
A1 Balaña, Carmen
A1 Gil-Gil, Miguel
A1 Reynes, Gaspar
A1 Gallego, Oscar
A1 Martinez-Garcia, Maria
A1 Vicente, Elena
A1 Quindos, Maria
A1 Luque, Raquel
A1 Ramos, Ana
A1 Ruano, Yolanda
A1 Perez-Segura, Pedro
A1 Benavides, Manuel
A1 Sanchez-Gomez, Pilar
A1 Hernandez-Lain, Aurelio
K1 EGFR
K1 Dacomitinib
K1 Glioblastoma
K1 High-grade glioma
AB 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 gene (EGFR) amplification with or without variant III (EGFRvIII) deletion. Patients with first recurrence were enrolled in 2 cohorts. Cohort A included patients with EGFR gene amplification without EGFRvIII mutation. Cohort B included patients with EGFR gene amplification and EGFRvIII mutation. Dacomitinib was administered (45 mg/day) until disease progression/unacceptable adverse events (AEs). Primary endpoint was progression-free survival (PFS; RANO criteria) at 6 months (PFS6). Thirty patients in Cohort A and 19 in Cohort B were enrolled. Median age was 59 years (range 39-81), 65.3% were male, and Eastern Cooperative Oncology Group Performance Status 0/1/2 were 10.2%/65.3%/24.5%, respectively. PFS6 was 10.6% (Cohort A: 13.3%; Cohort B: 5.9%) with a median PFS of 2.7 months (Cohort A: 2.7 mo; Cohort B: 2.6 mo). Four patients were progression free at 6 months and 3 patients were so at 12 months. Median overall survival was 7.4 months (Cohort A: 7.8 mo; Cohort B: 6.7 mo). The best overall response included 1 complete response and 2 partial responses (4.1%). Stable disease was observed in 12 patients (24.5%: eight in 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. 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 who could benefit from dacomitinib.
PB Oxford University Press
YR 2017
FD 2017-06-01
LK http://hdl.handle.net/10668/11264
UL http://hdl.handle.net/10668/11264
LA en
NO Sepúlveda-Sánchez JM, Vaz MÁ, Balañá C, Gil-Gil M, Reynés G, Gallego Ó, et al.  Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification. Neuro Oncol. 2017 Oct 19;19(11):1522-1531
DS RISalud
RD Apr 19, 2025