AVAGLIO

Background

AVAGLIO was a phase III, placebo-controlled RCT (n=921) testing whether adding bevacizumab (anti-VEGF mAb) to the standard Stupp protocol (RT + TMZ) improves outcomes in newly diagnosed GBM, based on the anti-angiogenic rationale in this highly vascular tumor.

Interventions and follow up

Arm A: Radiotherapy + temozolomide + bevacizumab 10mg/kg q2wk, then maintenance temozolomide + bevacizumab
Arm B: Radiotherapy + temozolomide + placebo, then maintenance temozolomide + placebo
Primary endpoint: co-primary investigator-assessed PFS and OS
mFollow-up: NR

Results

mPFS: 10.6 vs 6.2mo (HR 0.64, 95% CI 0.55–0.74, P<.001)
mOS: 16.8 vs 16.7mo (HR 0.88, 95% CI 0.76–1.02, P=.10) — no OS benefit
Subgroups: no MGMT, IDH, or other subgroup derived an OS benefit

Adverse events

Overall (grade ≥3): 66.8% vs 51.3%; AE-related discontinuation higher with bevacizumab
Bevacizumab-related: hypertension 17% vs 5%, thromboembolism 8% vs 5%, plus proteinuria, wound-healing complications, and GI perforation.

Conclusions

Bevacizumab improved PFS but not OS when added to the standard Stupp protocol in newly diagnosed GBM. RTOG 0825 independently confirmed these findings, definitively removing bevacizumab from first-line GBM standard of care.

Key Limitations

PFS gain likely confounded by bevacizumab's anti-permeability ('pseudoresponse') effect on contrast-enhanced MRI, complicating radiographic progression assessment. No OS benefit despite PFS improvement. Conducted before IDH/molecular reclassification of GBM.

Clinical Context

AVAGLIO and RTOG 0825 established that bevacizumab has no role in first-line GBM; ASCO/SNO and ESMO guidelines do not recommend it upfront. Bevacizumab retains a palliative role in recurrent GBM and for symptomatic management of edema, but without an OS benefit.

References