A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas

Karan S. Dixit*, Sean Sachdev, Christina Amidei, Priya Kumthekar, Tim J. Kruser, Vinai Gondi, Sean Grimm, Rimas V. Lukas, Martin Kelly Nicholas, Steven J. Chmura, Angela J. Fought, Minesh Mehta, Jeffrey J. Raizer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-naïve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial. Methods: Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55 Gy to enhancing disease, 45 Gy to non-enhancing disease in 25 fractions) with bevacizumab 10 mg/kg every 2 weeks IV and temozolomide 75 mg/m2 daily followed by maintenance bevacizumab 10 mg/kg every 2 weeks and temozolomide 50 mg/m2 daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales. Results: Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred. Conclusions: Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.

Original languageEnglish (US)
Pages (from-to)297-306
Number of pages10
JournalJournal of Neuro-Oncology
Volume155
Issue number3
DOIs
StatePublished - Dec 2021

Keywords

  • Bevacizumab
  • Glioblastoma
  • Radiation
  • Re-irradiation
  • Recurrent glioma
  • Temozolomide

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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