Researchers say they have identified a molecular signature that can be used to predict outcomes of regorafenib treatment in patients with recurrent glioblastoma.
The team found that patients with mutations in the MAPK pathway had inferior outcomes when compared with patients who had mutations in the EGFR pathway. The researchers presented these findings in a poster at the Society for Neuro-Oncology 27th Annual Meeting.
The researchers investigated potential molecular markers for regorafenib response in a cohort of 30 patients with IDH wild-type, recurrent glioblastoma. The patients underwent next-generation sequencing with a panel targeting 16 genes, a methylation analysis of MGMT, and an expression analysis of EGFRvIII.
The patients’ mean age was 58.4 years, the maximum tumor diameter was 3.6 cm, and 48.3% of patients underwent surgery at recurrence. Exactly half of patients were EGFRvIII-positive, and 41.4% had methylated MGMT promoter.
The sequencing analysis showed that 18% of patients had a mutation in the EGFR pathway, and 18% had a mutation in the MAPK pathway. No other mutations were observed.
The entire population had a 6-month progression-free survival (PFS) rate of 30% and a median overall survival (OS) of 7.5 months.
The patients who had mutations in the MAPK pathway had inferior PFS to patients with mutations in the EGFR pathway. The median PFS was 2.5 months and 4.5 months, respectively (P =.0061). The median OS was not significantly different between the groups — 7 months and 9 months, respectively (P =.1076).
However, when the researchers combined the sequencing and EGFRvIII analyses, they found that patients with an EGFR pathway activation had significantly better PFS (P =.0004) and OS (P =.0242) than patients who had MAPK pathway activation.
In a multivariate analysis, worse PFS with regorafenib was associated with MAPK pathway mutations (hazard ratio [HR], 5.485; 95% CI, 1.325-22.703; P =.0188), and better PFS was associated with the extent of resection (HR, 0.241; 95% CI, 0.065-0.889; P =.0326).
The researchers concluded that the MAPK-altered signature is “predictive of scarce response to regorafenib at recurrence” in patients with IDH wild-type glioblastoma.
Disclosures: The study authors did not provide disclosures.
Chiesa S, Mangraviti A, Martini M, et al. A study of clinical and molecular prognostic factors for response to regorafenib in recurrent glioblastoma. Presented at SNO 2022; November 16-20, 2022. Abstract BIOM-36.