Dataset Information

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

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).

SUBMITTER: Pouessel D

PROVIDER: S-EPMC10485381 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Pouessel Damien D Ken Soléakhéna S Gouaze-Andersson Valérie V Piram Lucie L Mervoyer Augustin A Larrieu-Ciron Delphine D Cabarrou Bastien B Lusque Amélie A Robert Marie M Frenel Jean-Sebastien JS Uro-Coste Emmanuelle E Olivier Pascale P Mounier Muriel M Sabatini Umberto U Sanchez Eduardo Hugo EH Zouitine Mehdi M Berjaoui Ahmad A Cohen-Jonathan Moyal Elizabeth E

The oncologist 20230901 9

<h4>Background</h4>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.<h4>Methods</h4>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 progres ...[more]

PMID: 37196069

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Project description:The combination of re-irradiation and bevacizumab has emerged as a potential therapeutic strategy for patients experiencing their first glioblastoma multiforme (GBM) recurrence. This study aims to assess the effectiveness of the re-irradiation and bevacizumab combination in treating second-progression GBM patients who are resistant to bevacizumab monotherapy. This retrospective study enrolled 64 patients who developed a second progression after single-agent bevacizumab therapy. The patients were divided into two groups: 35 underwent best supportive care (none-ReRT group), and 29 received bevacizumab and re-irradiation (ReRT group). The study measured the overall survival time after bevacizumab failure (OST-BF) and re-irradiation (OST-RT). Statistical tests were used to compare categorical variables, evaluate the difference in recurrence patterns between the two groups, and identify optimal cutoff points for re-irradiation volume. The results of the Kaplan-Meier survival analysis indicated that the re-irradiation (ReRT) group experienced a significantly higher survival rate and longer median survival time than the non-ReRT group. The median OST-BF and OST-RT were 14.5 months and 8.8 months, respectively, for the ReRT group, while the OST-BF for the none-ReRT group was 3.9 months (p < 0.001). The multivariable analysis identified the re-irradiation target volume as a significant factor for OST-RT. Moreover, the re-irradiation target volume exhibited excellent discriminatory ability in the area under the curve (AUC) analysis, with an optimal cutoff point of greater than 27.58 ml. These findings suggest that incorporating re-irradiation with bevacizumab therapy may be a promising treatment strategy for patients with recurrent GBM resistant to bevacizumab monotherapy. The re-irradiation target volume may serve as a valuable selection factor in determining which patients with recurrent GBM are likely to benefit from the combined re-irradiation and bevacizumab treatment modality.

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Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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

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