Repeated responders to bevacizumab combination treatment in recurrent glioblastoma: a retrospective case study.

Purpose: Bevacizumab combination treatment rechallenge in glioblastoma (GBM) patients who initially responded at recurrence has shown renewed responses in up to 60% of cases, with associated survival benefits. This study sought to characterise such repeat responders and identify predictive biomarkers.

Methods: A total of 254 IDHwt GBM patients treated with bevacizumab plus chemotherapy (BevCT) were evaluated for eligibility. Five patients met the inclusion criteria for this case study by exhibiting repeated responses to BevCT and having tumour tissue available for molecular analysis. Histopathological re-assessments were performed to confirm GBM diagnoses. Angiotensinogen (AGT) promoter methylation status was analysed in all primary tumour samples, while bulk RNA sequencing and TSO500 assays were conducted on all available samples.

Results: In our cohort, 40% of patients who were rechallenged with BevCT following a treatment pause exhibited a response both during the initial course and upon rechallenge. Bulk RNA sequencing revealed downregulation of HILPDA and IGF2 as potentially predictive of repeated bevacizumab response. Additionally, AGT promoter methylation analysis identified high methylation levels as another potential predictive biomarker.

Conclusions: A subgroup of GBM patients responds to BevCT up to three times in the recurrent setting, and these repeated responders exhibit prolonged survival. No definitive prognostic variables or histopathological features were found in this study. Further investigation into the downregulation of HILPDA and IGF2, along with high AGT promoter methylation levels and other potential predictive biomarkers, is warranted to better understand the mechanisms underlying repeated BevCT response.