Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification
Por:
Sepulveda-Sanchez, JM, Vaz, MA, Balana, C, Gil-Gil, M, Reynes, G, Gallego, O, Martinez-Garcia, M, Vicente, E, Quindos, M, Luque, R, Ramos, A, Ruano, Y, Perez-Segura, P, Benavides, M, Sanchez-Gomez, P, Hernandez-Lain, A
Publicada:
1 nov 2017
Resumen:
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 gene (EGFR) amplification with or without variant III (EGFRvIII) deletion. Methods. 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). Results. 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. Conclusions. 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.
Filiaciones:
Sepulveda-Sanchez, JM:
Hosp Univ 12 Octubre, Neurooncol Unit, Madrid, Spain
Vaz, MA:
Hosp Univ Ramon & Cajal, Med Oncol, Madrid, Spain
Balana, C:
Inst Catala Oncol, Med Oncol, Badalona, Spain
Gil-Gil, M:
IDIBELL, Inst Catala Oncol, Med Oncol, Barcelona, Spain
Reynes, G:
Hosp Univ & Politecn La Fe, Med Oncol, Valencia, Spain
Gallego, O:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Med Oncol, Barcelona, Spain
Martinez-Garcia, M:
Hosp del Mar, Med Oncol, Barcelona, Spain
Vicente, E:
Hosp Univ Insular Gran Canaria, Med Oncol, Las Palmas Gran Canaria, Spain
Quindos, M:
Hosp A Coruna, Med Oncol, La Coruna, Spain
Luque, R:
Complejo Hosp Granada, Med Oncol, Granada, Spain
Ramos, A:
Hosp Univ 12 Octubre, Neuroradiol, Madrid, Spain
Ruano, Y:
Hosp Univ 12 Octubre, Mol Pathol Unit, Madrid, Spain
Perez-Segura, P:
Hosp Clin San Carlos, Med Oncol, Madrid, Spain
Benavides, M:
Hosp Univ Reg & Virgen de la Victoria, Med Oncol, Malaga, Spain
Sanchez-Gomez, P:
Inst Salud Carlos III, Neurooncol Unit, Madrid, Spain
Hernandez-Lain, A:
Hosp Univ 12 Octubre, Neuropathol, Madrid, Spain
Green Published, Bronze
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