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Open Access 01-10-2024 | Bevacizumab | Research

Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis

Authors: Guangzhong Guo, Ziyue Zhang, Jiubing Zhang, Dayang Wang, Sensen Xu, Guanzheng Liu, Yushuai Gao, Jie Mei, Zhaoyue Yan, Ruijiao Zhao, Meiyun Wang, Tianxiao Li, Xingyao Bu

Published in: Cancer Immunology, Immunotherapy | Issue 10/2024

Abstract

Objective

Most recurrent glioblastoma (rGBM) patients do not benefit from immune checkpoint inhibition, emphasizing the necessity for response biomarkers. This study evaluates whether tumor in situ fluid (TISF) circulating tumor DNA (ctDNA) could serve as a biomarker for response to low-dose bevacizumab (Bev) plus anti-PD-1 therapy in rGBM patients, aiming to enhance systemic responses to immunotherapy.

Methods

In this phase II trial, 32 GBM patients with first recurrence after standard therapy were enrolled and then received tislelizumab plus low-dose Bev each cycle. TISF samples were analyzed for ctDNA using a 551-gene panel before each treatment.

Results

The median progression-free survival (mPFS) and overall survival (mOS) were 8.2 months (95% CI, 5.2–11.1) and 14.3 months (95% CI, 6.5–22.1), respectively. The 12-month OS was 43.8%, and the objective response rate was 56.3%. Patients with more than 20% reduction in the mutant allele fraction and tumor mutational burden after treatment were significantly associated with better prognosis compared to baseline TISF-ctDNA. Among detectable gene mutations, patients with MUC16 mutation, EGFR mutation & amplification, SRSF2 amplification, and H3F3B amplification were significantly associated with worse prognosis.

Conclusions

Low-dose Bev plus anti-PD-1 therapy significantly improves OS in rGBM patients, offering guiding significance for future individualized treatment strategies. TISF-ctDNA can monitor rGBM patients' response to combination therapy and guide treatment.

Clinical trial registration

This trial is registered with ClinicalTrials.gov, NCT05540275.

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Title: Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis
Authors: Guangzhong Guo
Ziyue Zhang
Jiubing Zhang
Dayang Wang
Sensen Xu
Guanzheng Liu
Yushuai Gao
Jie Mei
Zhaoyue Yan
Ruijiao Zhao
Meiyun Wang
Tianxiao Li
Xingyao Bu
Publication date: 01-10-2024
Publisher: Springer Berlin Heidelberg
Keywords: Bevacizumab
Glioblastoma
Glioblastoma
Glioblastoma
Biomarkers
Published in: Cancer Immunology, Immunotherapy / Issue 10/2024
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-024-03774-7

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Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis

Abstract

Objective

Methods

Results

Conclusions

Clinical trial registration

2024 ESMO Congress

Add-on Ra223 could be a new first-line option in mCRPC

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No OS benefit of adding preoperative CRT in gastric cancer

T-DXd supported for breast cancer with brain metastases

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Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

Live event concluded

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Abstract

Objective

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Clinical trial registration

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