Journal Article

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

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

2024

Overview

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.

• Publisher: Oxford University Press
• Subject: Adult / Aged / Antineoplastic Agents, Immunological - adverse effects / Antineoplastic Agents, Immunological - therapeutic use / Brain Neoplasms - drug therapy / Brain Neoplasms - genetics / Dosage and administration / Drug therapy / Female / Genetic aspects / Glioblastoma - drug therapy / Glioblastoma - genetics / Glioblastoma - mortality / Glioblastoma - pathology / Glioblastoma multiforme / Glioma / Humans / Male / Medical prognosis / Middle Aged / Panitumumab / Panitumumab - adverse effects / Panitumumab - pharmacology / Panitumumab - therapeutic use / Patient outcomes / raf Kinases - antagonists & inhibitors / raf Kinases - genetics / ras Proteins - genetics