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- Title
Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma: Results From the Drug Rediscovery Protocol.
- Authors
Spiekman, Ilse A C; Geurts, Birgit S; Zeverijn, Laurien J; Wit, Gijs F de; van der Noort, Vincent; Roepman, Paul; Leng, Wendy W J de; Jansen, Anne M L; Kusters, Benno; Beerepoot, Laurens V; Vos, Filip Y F L de; Groot, Derk-Jan A de; Groot, Jan Willem B de; Hoeben, Ann; Buter, Jan; Gelderblom, Hans A J; Voest, Emile E; Verheul, Henk M W
- 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 / RAS wt glioblastoma precluding further development of this therapeutic strategy.
- Subjects
PROTEIN metabolism; THERAPEUTIC use of monoclonal antibodies; GLIOMAS; PATIENT safety; CLINICAL trials; DESCRIPTIVE statistics; PANITUMUMAB; LONGITUDINAL method; DRUG efficacy; RESEARCH; TRANSFERASES; SURVIVAL analysis (Biometry); CONFIDENCE intervals; EPIDERMAL growth factor receptors; EVALUATION
- Publication
Oncologist, 2024, Vol 29, Issue 5, p431
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyad320