학술논문
Hypofractionated Stereotactic Re-irradiation and Anti-PDL1 Durvalumab Combination in Recurrent Glioblastoma: STERIMGLI Phase I Results
Clinical Trial Results
Clinical Trial Results
Document Type
Report
Author
Pouessel, Damien; Ken, Soleakhena; Gouaze-Andersson, Valerie; Piram, Lucie; Mervoyer, Augustin; Larrieu-Ciron, Delphine; Cabarrou, Bastien; Lusque, Amelie; Robert, Marie; Frenel, Jean-Sebastien; Uro-Coste, Emmanuelle; Olivier, Pascale; Mounier, Muriel; Sabatini, Umberto; Sanchez, Eduardo Hugo; Zouitine, Mehdi; Berjaoui, Ahmad; Moyal, Elizabeth Cohen-Jonathan
Source
The Oncologist. September 2023, Vol. 28 Issue 9, p825, 15 p.
Subject
Language
English
ISSN
1083-7159
Abstract
Lessons Learned * The combination of hypofractionated stereotactic re-irradiation with Durvalumab for patients with recurrent gliobalstoma shows good tolerance with encouraging clinical response. * Patients with the best responses were [...]
Background: Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize antiPDL1 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). Key words: recurrent glioblastoma; hypofractionated stereotactic re-irradiation; Durvalumab; deep learning; phase I clinical trial.
Background: Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize antiPDL1 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). Key words: recurrent glioblastoma; hypofractionated stereotactic re-irradiation; Durvalumab; deep learning; phase I clinical trial.