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 V
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
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press.
PY - 2024/5/3
Y1 - 2024/5/3
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.
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.
KW - RAF/RAS-wildtype
KW - DRUP trial
KW - glioblastoma
KW - panitumumab
KW - precision medicine
UR - http://www.scopus.com/inward/record.url?scp=85192044478&partnerID=8YFLogxK
U2 - 10.1093/oncolo/oyad320
DO - 10.1093/oncolo/oyad320
M3 - Article
C2 - 38109296
VL - 29
SP - 431
EP - 440
JO - The oncologist
JF - The oncologist
IS - 5
ER -