Hypofractionated Stereotactic Re-irradiation and Anti-PDL1 Durvalumab Combination in Recurrent Glioblastoma: STERIMGLI Phase I Results

Autor: Damien Pouessel, Soléakhéna Ken, Valérie Gouaze-Andersson, Lucie Piram, Augustin Mervoyer, Delphine Larrieu-Ciron, Bastien Cabarrou, Amélie Lusque, Marie Robert, Jean-Sebastien Frenel, Emmanuelle Uro-Coste, Pascale Olivier, Muriel Mounier, Umberto Sabatini, Eduardo Hugo Sanchez, Mehdi Zouitine, Ahmad Berjaoui, Elizabeth Cohen-Jonathan Moyal
Rok vydání: 2023
Předmět:
Zdroj: The Oncologist.
ISSN: 1549-490X
1083-7159
DOI: 10.1093/oncolo/oyad095
Popis: Background Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB. Methods Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected. Results Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only. Conclusion Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).
Databáze: OpenAIRE
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