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Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma: Results From the Drug Rediscovery Protocol.
Spiekman, Ilse A C; Geurts, Birgit S; Zeverijn, Laurien J; de Wit, Gijs F; van der Noort, Vincent; Roepman, Paul; de Leng, Wendy W J; Jansen, Anne M L; Kusters, Benno; Beerepoot, Laurens V; de Vos, Filip Y F L; de Groot, Derk-Jan A; de Groot, Jan Willem B; Hoeben, Ann; Buter, Jan; Gelderblom, Hans A J; Voest, Emile E; Verheul, Henk M W.
Afiliación
  • Spiekman IAC; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
  • Geurts BS; Oncode Institute, Utrecht, The Netherlands.
  • Zeverijn LJ; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • de Wit GF; Oncode Institute, Utrecht, The Netherlands.
  • van der Noort V; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Roepman P; Oncode Institute, Utrecht, The Netherlands.
  • de Leng WWJ; Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Jansen AML; Department of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Kusters B; Hartwig Medical Foundation, Amsterdam, The Netherlands.
  • Beerepoot LV; Department of Pathology, University Medical Cancer Center Utrecht, Utrecht, The Netherlands.
  • de Vos FYFL; Department of Pathology, University Medical Cancer Center Utrecht, Utrecht, The Netherlands.
  • de Groot DA; Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • de Groot JWB; Department of Internal Medicine, ETZ Hospital (Elisabeth-TweeSteden Ziekenhuis), Tilburg, The Netherlands.
  • Hoeben A; Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Buter J; Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands.
  • Gelderblom HAJ; Isala Oncology Center, Isala, Zwolle, The Netherlands.
  • Voest EE; Division of Medical Oncology, Department of Internal Medicine, GROW School of Oncology and Development Biology, Maastricht University Center+, Maastricht, The Netherlands.
  • Verheul HMW; Department of Medical Oncology, Amsterdam University Medical Center, Location VuMC, Amsterdam, The Netherlands.
Oncologist ; 29(5): 431-440, 2024 May 03.
Article en En | MEDLINE | ID: mdl-38109296
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glioblastoma / Panitumumab Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Oncologist Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glioblastoma / Panitumumab Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Oncologist Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido