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

Autor:	Spiekman IAC; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands., Geurts BS; Oncode Institute, Utrecht, The Netherlands.; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Zeverijn LJ; Oncode Institute, Utrecht, The Netherlands.; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., de Wit GF; Oncode Institute, Utrecht, The Netherlands.; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., van der Noort V; Department of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands., Roepman P; Hartwig Medical Foundation, Amsterdam, The Netherlands., de Leng WWJ; Department of Pathology, University Medical Cancer Center Utrecht, Utrecht, The Netherlands., Jansen AML; Department of Pathology, University Medical Cancer Center Utrecht, Utrecht, The Netherlands., Kusters B; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., Beerepoot LV; Department of Internal Medicine, ETZ Hospital (Elisabeth-TweeSteden Ziekenhuis), Tilburg, The Netherlands., de Vos FYFL; Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., de Groot DA; Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands., de Groot JWB; Isala Oncology Center, Isala, Zwolle, The Netherlands., Hoeben A; Division of Medical Oncology, Department of Internal Medicine, GROW School of Oncology and Development Biology, Maastricht University Center+, Maastricht, The Netherlands., Buter J; Department of Medical Oncology, Amsterdam University Medical Center, Location VuMC, Amsterdam, The Netherlands., Gelderblom HAJ; Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands., Voest EE; Oncode Institute, Utrecht, The Netherlands.; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Center for Personalized Cancer Treatment, Rotterdam,The Netherlands., Verheul HMW; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	The oncologist [Oncologist] 2024 May 03; Vol. 29 (5), pp. 431-440.
DOI:	10.1093/oncolo/oyad320
Abstrakt:	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. (© The Author(s) 2023. Published by Oxford University Press.)
Databáze:	MEDLINE
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