Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma: Results From the Drug Rediscovery Protocol

Ilse A. C. Spiekman, Birgit S. Geurts, Laurien J. Zeverijn, Gijs F. de Wit, Vincent van der Noort, Paul Roepman, Wendy W. J. de Leng, Anne M. L. Jansen, Benno Kusters, Laurens Beerepoot, Filip Y. F. L. de Vos, Derk-Jan A. de Groot, Jan Willem B. de Groot, Ann Hoeben, Jan Buter, Hans A. J. Gelderblom, Emile E. Voest, Henk M. W. Verheul*

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article numberoyad320
Pages (from-to)431-440
Number of pages10
JournalOncologist
Volume29
Issue number5
Early online date18 Dec 2023
DOIs
Publication statusPublished - 3 May 2024

Bibliographical note

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© 2023 The Author(s). Published by Oxford University Press.

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