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Tumor response based on adapted Macdonald criteria and assessment of pseudoprogression (PsPD) in the phase III AVAglio trial of bevacizumab (Bv) plus temozolomide (T) plus radiotherapy (RT) in newly diagnosed glioblastoma (GBM).
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Background: Until recently the primary criteria for assessing response to GBM therapy were those by Macdonald et al. (JCO 1990;8:1277–80). Advances in imaging technology/targeted therapies exposed limitations, addressed in 2010 by Response Assessment in Neuro-Oncology Working Group. Prior to this, the AVAglio study similarly adapted Macdonald criteria to address anti-angiogenic therapy/corticosteroid use by incorporating non-contrast-enhancing components and integrating a strict algorithm to standardize assessment of possible PsPD. Methods: Randomisedpts (n=921) received: T/RT + Bv or placebo (P), 6 wks; 28-d break; maintenance T + Bv or P (6 cycles); monotherapy Bv or P until PD/unacceptable toxicity. Tumor response was investigator (inv)-assessed by MRI (adapted Macdonald criteria) at baseline (BL), end of break, every 2nd maintenance cycle, every 9 wks during monotherapy, at PD and 9 wks post-PD. PsPD was inv-assessed at the end of the break. A ≥25% increase in index lesions and/or unequivocal progression of existing non-index lesions relative to BL and in the absence of clinical deterioration was assessed as PsPD. Confirmatory PsPD assessment: end of the 2nd maintenance cycle. If progression was confirmed, PsPD was retrospectively designated as PD. If PsPD was confirmed, pts remained on treatment and the 1st post-RT MRI was used as a new BL. Best ORR was evaluated in pts with lesions at BL, excluding pts with confirmed PsPD. Results: Co-primary endpoint of inv-assessed PFS was longer for pts receiving Bv+RT/T compared with P+RT/T (HR 0.64, 95% CI 0.55–0.74; p<0.0001). Best ORR and PsPD are shown (Table). Conclusions: Addition of Bv to 1st-line T/RT significantly improves ORR. The rate of confirmed PsPD was low in both arms. Clinical trial information: NCT00943826.
% (95% CI)
|Difference, % (95% CI)||20.4 (13.9–26.8)|
|End of treatment break|
|Potential PsPD, n (%)||12 (2.6)||84 (18.1)|
|Post-2nd maintenance cycle|
|Confirmed PsPD, n (%)||10 (2.2)||43 (9.3)|
|Rejected PsPD, n (%)||1 (0.2)||35 (7.6)|
|Missing, n (%)||1 (0.2)||6 (1.3)|
Abstracts by W. Wick:
AVAglio: A phase III trial of bevacizumab added to standard radiotherapy and temozolomide in patients with newly diagnosed glioblastoma.Meeting: 2011 ASCO Annual Meeting | Abstract No: TPS136
Enzastaurin (ENZ) before and concomitant with radiation therapy (RTX) followed by ENZ maintenance therapy in patients with newly diagnosed glioblastoma (GBM) without hypermethylation of the O6-methylguanyl DNA-methyltransferase (MGMT) promoter: A multicenter, open-label, uncontrolled phase II study.Meeting: 2011 ASCO Annual Meeting | Abstract No: 2007