Prognostic impact of hand-foot skin reaction in regorafenib-treated adult-type diffuse gliomas: A multicenter Turkish Oncology Group study

Glioblastoma, IDH-wildtype is the most aggressive primary brain tumor in adults, and treatment options for recurrent disease are limited. Regorafenib, an oral multikinase inhibitor, has shown efficacy in glioblastoma at first recurrence, but its role in later recurrences and in other adult-type diffuse gliomas remains unclear. This multicenter retrospective study aimed to evaluate the safety and efficacy of regorafenib and to identify prognostic factors in patients with adult-type diffuse gliomas, including glioblastoma, who were treated at the second or subsequent recurrences. A total of 68 patients from 22 institutions were analyzed. The median overall survival (OS) was 3.84 months, and the median progression-free survival was 2.46 months. The objective response rate was 13%, and the disease control rate was 48%. Adverse events occurred in 80.9% of patients, most commonly fatigue, anemia, and elevated transaminases. Hand-foot skin reaction (HFSR) of any grade was observed in 36.4% of patients and was associated with significantly improved OS (HR: 0.41; p = 0.005). Regorafenib demonstrated a manageable safety profile and modest activity in this heavily pretreated population. The development of HFSR emerged as a potential prognostic marker for treatment benefit. Taken together, our findings support further exploration of regorafenib in this setting and suggest that HFSR may serve as a practical marker to guide treatment continuation.

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Publication Details

Journal
Scientific Reports
Published
2025-10-16
DOI
https://doi.org/10.1038/s41598-025-19899-3
Primary Topic
Glioma Diagnosis and Treatment
Type
article
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article

Prognostic impact of hand-foot skin reaction in regorafenib-treated adult-type diffuse gliomas: A multicenter Turkish Oncology Group study

Sema Türker, Mesut Yılmaz, Gamze Gököz Doğu, Bilgeşah Kılıçtaş et al.
Scientific Reports
Glioma Diagnosis and Treatment
article

Prognostic impact of hand-foot skin reaction in regorafenib-treated adult-type diffuse gliomas: A multicenter Turkish Oncology Group study

Sema Türker, Mesut Yılmaz, Gamze Gököz Doğu, Bilgeşah Kılıçtaş, Özkan Alan, Nejat Emre Öksüz, Mustafa Şahbazlar, Nagihan Kolkıran, Neyran Kertmen, Burak Bi̇lgi̇n, Orhun Akdoğan, Safa Can Efil, Taha Koray Şahin, Ali Kaan Güren, Teoman Şakalar, Mehmet Alı Nahıt Şendur, Evren Fidan, Aziz Batu, Efnan Algın, İrem Bilgetekin, Erdinç Nayır, Mehmet Artaç, Ertuğrul Bayram, Engin Kut, Kaan Helvacı, Elif Şahin, Ozan Yazıcı, Ahmet Melih Arslan, Ceren Mordağ Çiçek, Sedat Biter, Bülent Yalçın, Sinem Akbaş, Esra Aşık, Yüksel Urun, Fatma Esra Erdem Palaz
article en

Abstract

Glioblastoma, IDH-wildtype is the most aggressive primary brain tumor in adults, and treatment options for recurrent disease are limited. Regorafenib, an oral multikinase inhibitor, has shown efficacy in glioblastoma at first recurrence, but its role in later recurrences and in other adult-type diffuse gliomas remains unclear. This multicenter retrospective study aimed to evaluate the safety and efficacy of regorafenib and to identify prognostic factors in patients with adult-type diffuse gliomas, including glioblastoma, who were treated at the second or subsequent recurrences. A total of 68 patients from 22 institutions were analyzed. The median overall survival (OS) was 3.84 months, and the median progression-free survival was 2.46 months. The objective response rate was 13%, and the disease control rate was 48%. Adverse events occurred in 80.9% of patients, most commonly fatigue, anemia, and elevated transaminases. Hand-foot skin reaction (HFSR) of any grade was observed in 36.4% of patients and was associated with significantly improved OS (HR: 0.41; p = 0.005). Regorafenib demonstrated a manageable safety profile and modest activity in this heavily pretreated population. The development of HFSR emerged as a potential prognostic marker for treatment benefit. Taken together, our findings support further exploration of regorafenib in this setting and suggest that HFSR may serve as a practical marker to guide treatment continuation.

Scientific ReportsVol. 15(1)
Toros University (TR), Bahçeşehir University (TR), Koç University (TR), Ankara University (TR), Karadeniz Technical University (TR), Manisa Celal Bayar University (TR), Bilkent University (TR), Dokuz Eylül University (TR), Memorial Ankara Hospital (TR), Necmettin Erbakan University (TR), Ümraniye Eğitim ve Araştırma Hastanesi (TR), Istanbul University-Cerrahpaşa (TR), Sakarya Eğitim ve Araştırma Hastanesi (TR), Başkent University Hospital (TR), Ankara Bilkent City Hospital (TR), Kahramanmaraş Sütçü İmam University (TR), Pamukkale University (TR), Mersin Üniversitesi (TR), Kocaeli Üniversitesi (TR), Cukurova University (TR), Hacettepe University (TR), Istanbul University (TR), Marmara University (TR), Gazi University (TR)
Openalex Percentile: Top 59%
Glioma Diagnosis and Treatment
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