Abstract
Abstract Background Our previous clinical investigation suggested that hypofractionated stereotactic re-irradiation (HFSRT) and PD-1 blockade may act synergistically to enhance the immune response against glioma. This subsequent trial investigated the dual blockade of CTLA4 and PD-1 in combination with HFSRT and bevacizumab. Methods This phase I study enrolled eligible patients with bevacizumab-naïve recurrent glioblastoma or anaplastic astrocytoma. Participants received nivolumab, ipilimumab and bevacizumab concurrently with HFSRT (3000 cGy in 5 fractions). Subsequently, nivolumab, ipilimumab and bevacizumab were administered for a total of 4 cycles followed by nivolumab and bevacizumab until progression. The primary end point of this study was safety and tolerability of HFSRT in combination with nivolumab, ipilimumab, and bevacizumab in patients with recurrent HGGs. Secondary end points included 6-months survival and 9-months survival. Results Twenty-six patients were treated. Treatment-related adverse events (TRAEs) of grade 3 or 4 were observed in 12 (48%) of evaluable patients with no unexpected TRAEs. Six-months and 9-months survival were 92% (95% CI, 82 to 100%) and 75% (95% CI, 60 to 95%), respectively. The median progression-free survival and overall survival were 7.1 months (95% CI, 5.2–12.2) and 15.6 months (95% CI, 11.3–27.0), respectively. Conclusions The combination of HFSRT with ipilimumab, nivolumab and bevacizumab is safe. Our results underscore the potential synergies between stereotactic re-irradiation and checkpoint immunotherapy in patients with recurrent high-grade gliomas.
Published Version
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