TY - JOUR
T1 - Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma
T2 - Results From the Drug Rediscovery Protocol
AU - Spiekman, Ilse A. C.
AU - Geurts, Birgit S.
AU - Zeverijn, Laurien J.
AU - de Wit, Gijs F.
AU - van der Noort, Vincent
AU - Roepman, Paul
AU - de Leng, Wendy W. J.
AU - Jansen, Anne M. L.
AU - Kusters, Benno
AU - Beerepoot, Laurens
AU - de Vos, Filip Y. F. L.
AU - de Groot, Derk-Jan A.
AU - de Groot, Jan Willem B.
AU - Hoeben, Ann
AU - Buter, Jan
AU - Gelderblom, Hans A. J.
AU - Voest, Emile E.
AU - Verheul, Henk M. W.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Background The prognosis of malignant primary high-grade brain tumors, predominantly glioblastomas, is poor despite intensive multimodality treatment options. In more than 50% of patients with glioblastomas, potentially targetable mutations are present, including rearrangements, altered splicing, and/or focal amplifications of epidermal growth factor receptor (EGFR) by signaling through the RAF/RAS pathway. We studied whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS-wild-type (wt) glioblastomas in the Drug Rediscovery Protocol (DRUP).Methods Patients with progression of treatment refractory RAF/RASwt glioblastoma were included for treatment with panitumumab in DRUP when measurable according to RANO criteria. The primary endpoints of this study are clinical benefit (CB: defined as confirmed objective response [OR] or stable disease [SD] >= 16 weeks) and safety. Patients were enrolled using a Simon-like 2-stage model, with 8 patients in stage 1 and up to 24 patients in stage 2 if at least 1 in 8 patients had CB in stage 1.Results Between 03-2018 and 02-2022, 24 evaluable patients were treated. CB was observed in 5 patients (21%), including 2 patients with partial response (8.3%) and 3 patients with SD >= 16 weeks (12.5%). After median follow-up of 15 months, median progression-free survival and overall survival were 1.7 months (95% CI 1.6-2.1 months) and 4.5 months (95% CI 2.9-8.6 months), respectively. No unexpected toxicities were observed.Conclusions Panitumumab treatment provides limited CB in patients with recurrent RAF/RASwt glioblastoma precluding further development of this therapeutic strategy.New treatment options are needed for patients with recurrent glioblastomas. This study focused on whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS -wild-type glioblastomas in the Drug Rediscovery Protocol.
AB - Background The prognosis of malignant primary high-grade brain tumors, predominantly glioblastomas, is poor despite intensive multimodality treatment options. In more than 50% of patients with glioblastomas, potentially targetable mutations are present, including rearrangements, altered splicing, and/or focal amplifications of epidermal growth factor receptor (EGFR) by signaling through the RAF/RAS pathway. We studied whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS-wild-type (wt) glioblastomas in the Drug Rediscovery Protocol (DRUP).Methods Patients with progression of treatment refractory RAF/RASwt glioblastoma were included for treatment with panitumumab in DRUP when measurable according to RANO criteria. The primary endpoints of this study are clinical benefit (CB: defined as confirmed objective response [OR] or stable disease [SD] >= 16 weeks) and safety. Patients were enrolled using a Simon-like 2-stage model, with 8 patients in stage 1 and up to 24 patients in stage 2 if at least 1 in 8 patients had CB in stage 1.Results Between 03-2018 and 02-2022, 24 evaluable patients were treated. CB was observed in 5 patients (21%), including 2 patients with partial response (8.3%) and 3 patients with SD >= 16 weeks (12.5%). After median follow-up of 15 months, median progression-free survival and overall survival were 1.7 months (95% CI 1.6-2.1 months) and 4.5 months (95% CI 2.9-8.6 months), respectively. No unexpected toxicities were observed.Conclusions Panitumumab treatment provides limited CB in patients with recurrent RAF/RASwt glioblastoma precluding further development of this therapeutic strategy.New treatment options are needed for patients with recurrent glioblastomas. This study focused on whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS -wild-type glioblastomas in the Drug Rediscovery Protocol.
KW - glioblastoma
KW - RAF/RAS-wildtype
KW - panitumumab
KW - precision medicine
KW - DRUP trial
KW - GROWTH-FACTOR RECEPTOR
KW - PHASE-II TRIAL
KW - CENTRAL-NERVOUS-SYSTEM
KW - MONOCLONAL-ANTIBODY
KW - ACQUIRED-RESISTANCE
KW - PRIMARY BRAIN
KW - CANCER
KW - TUMORS
KW - TEMOZOLOMIDE
KW - BEVACIZUMAB
U2 - 10.1093/oncolo/oyad320
DO - 10.1093/oncolo/oyad320
M3 - Article
SN - 1083-7159
JO - Oncologist
JF - Oncologist
M1 - oyad320
ER -