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

Oncologist. 2023 Sep 7;28(9):825-e817. doi: 10.1093/oncolo/oyad095.

Abstract

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).

Keywords: Durvalumab; deep learning; hypofractionated stereotactic re-irradiation; phase I clinical trial; recurrent glioblastoma.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / radiotherapy
  • Cytokines
  • Glioblastoma* / drug therapy
  • Glioblastoma* / radiotherapy
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / radiotherapy
  • Radiosurgery* / adverse effects
  • Re-Irradiation*
  • Treatment Outcome

Substances

  • durvalumab
  • atezolizumab
  • Cytokines

Associated data

  • ClinicalTrials.gov/NCT02866747