NRG-BN010 immuno-RT combination failed to improve response in recurrent glioblastoma

KEY POINTS

• NRG-BN010 was a multicentre phase II trial evaluating tocilizumab, atezolizumab and fractionated stereotactic reirradiation for first recurrent glioblastoma. A total of 41 patients were eligible and evaluable across 19 sites.
• The safety run-in established the final regimen as tocilizumab 8 mg/kg plus atezolizumab 1680 mg every 28 days, with FSRT delivered 3–7 days after the first systemic dose as 24 Gy in 3 fractions.
• The phase II non-surgical cohort included 29 patients. The primary endpoint was objective response by modified RANO criteria, with the trial designed to distinguish a response rate of ≤10% from one of ≥30%.
• The efficacy target was clearly missed. Only 1/29 patients responded, for an objective response rate of 3.4% (95% CI 0.1–17.8%), and the regimen did not meet the prespecified threshold for further testing in this setting.
• Median progression-free survival was 3.2 months, with 6-month PFS of 20.7%. Median overall survival was 10.2 months, with 6-month OS of 78.6%. These outcomes did not suggest a substantial improvement over expected recurrent-GBM results.
• Safety was sufficient to deliver the triplet regimen. Only one protocol-defined dose-limiting toxicity occurred during the run-in, at a lower dose level; none occurred at the final combination dose. Common treatment-related toxicities included fatigue, liver-test abnormalities, cytopenias and headache.
• All-cause severe adverse events remained frequent in this recurrent-GBM population: 55.2% had grade 3, 6.9% grade 4 and 6.9% grade 5 events in the phase II cohort, although these figures were reported irrespective of treatment attribution. The authors found no major signal of radiation necrosis with the 3-fraction reirradiation approach.

CLINICAL TAKEAWAY

SOURCE

International Journal of Radiation Oncology, Biology, Physics