Wolfgang Wick1, Olivier L Chinot2, Martin Bendszus2, Warren Mason2, Roger Henriksson2, Frank Saran2, Ryo Nishikawa2, Cedric Revil2, Yannick Kerloeguen2, Timothy Cloughesy2. 1. University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.) wolfgang.wick@med.uni-heidelberg.de. 2. University Medical Center, Heidelberg, Germany (W.W., M.B.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Princess Margaret Hospital, * Toronto, Canada (W.M.); Regional Cancer Center Stockholm Gotland, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden (R.H.); The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Saitama Medical University, Iruma, Saitama Prefecture, Japan (R.N.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (C.R., Y.K.); University of California Los Angeles, Los Angeles, California (T.C.).
Abstract
BACKGROUND: Evaluation of glioblastoma disease status may be complicated by treatment-induced changes and discordance between enhancing and nonenhancing MRI. Exploratory analyses are presented (prospectively assessed pseudoprogression and therapy-related tumor pattern changes) from the AVAglio trial (bevacizumab or placebo plus radiotherapy/temozolomide for newly diagnosed glioblastoma). METHODS: MRI was done every 8 weeks (beginning 4 wk after chemoradiotherapy) using prespecified and standardized T1 and T2 protocols. Progressive disease (PD) at 10 weeks was reconfirmed at 18 weeks to distinguish pseudoprogression. Progression-free survival (PFS), excluding cases of confirmed pseudoprogression, was assessed (post-hoc/exploratory). Tumor progression patterns were determined at each disease assessment/PD (prespecified/exploratory). RESULTS: Of patients with PD in the bevacizumab and placebo arms, 143/354 (40.4%) and 155/387 (40.1%), respectively, had PD due to contrast-enhancing lesions, and 51/354 (14.4%) and 53/387 (13.7%) had PD due to nonenhancing lesions. Of all patients in the bevacizumab arm (n = 458), 2.2% had confirmed pseudoprogression versus 9.3% in the placebo arm (n = 463). Baseline characteristics did not differ between patients with/without pseudoprogression (including for MGMT status). Excluding confirmed pseudoprogression, PFS (hazard ratio: 0.65, 95% CI: 0.56-0.75; P < .0001, bevacizumab vs placebo) was comparable to the intent-to-treat population. At PD, most patients had the same tumor focus (local/multifocal, >84%) and infiltrative profile (>88%) as at baseline; no shift to a diffuse or multifocal phenotype was observed. CONCLUSIONS: Pseudoprogression complicated progression assessment in a small but relevant number of patients but had negligible impact on PFS. Bevacizumab did not appear to adversely impact tumor progression patterns.
RCT Entities:
BACKGROUND: Evaluation of glioblastoma disease status may be complicated by treatment-induced changes and discordance between enhancing and nonenhancing MRI. Exploratory analyses are presented (prospectively assessed pseudoprogression and therapy-related tumor pattern changes) from the AVAglio trial (bevacizumab or placebo plus radiotherapy/temozolomide for newly diagnosed glioblastoma). METHODS: MRI was done every 8 weeks (beginning 4 wk after chemoradiotherapy) using prespecified and standardized T1 and T2 protocols. Progressive disease (PD) at 10 weeks was reconfirmed at 18 weeks to distinguish pseudoprogression. Progression-free survival (PFS), excluding cases of confirmed pseudoprogression, was assessed (post-hoc/exploratory). Tumor progression patterns were determined at each disease assessment/PD (prespecified/exploratory). RESULTS: Of patients with PD in the bevacizumab and placebo arms, 143/354 (40.4%) and 155/387 (40.1%), respectively, had PD due to contrast-enhancing lesions, and 51/354 (14.4%) and 53/387 (13.7%) had PD due to nonenhancing lesions. Of all patients in the bevacizumab arm (n = 458), 2.2% had confirmed pseudoprogression versus 9.3% in the placebo arm (n = 463). Baseline characteristics did not differ between patients with/without pseudoprogression (including for MGMT status). Excluding confirmed pseudoprogression, PFS (hazard ratio: 0.65, 95% CI: 0.56-0.75; P < .0001, bevacizumab vs placebo) was comparable to the intent-to-treat population. At PD, most patients had the same tumor focus (local/multifocal, >84%) and infiltrative profile (>88%) as at baseline; no shift to a diffuse or multifocal phenotype was observed. CONCLUSIONS: Pseudoprogression complicated progression assessment in a small but relevant number of patients but had negligible impact on PFS. Bevacizumab did not appear to adversely impact tumor progression patterns.
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