title: Upfront bevacizumab may extend survival for glioblastoma patients who do not receive second-line therapy: an exploratory analysis of AVAglio.
abstract: In this post-hoc, exploratory analysis, we examined outcomes for patients enrolled in the AVAglio trial of front-line bevacizumab or placebo plus radiotherapy/temozolomide who received only a single line of therapy.
  
  
  
  Patients with newly diagnosed glioblastoma received protocol-defined treatment until progressive disease (PD). Co-primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). After confirmed PD, patients were treated at the investigators' discretion. PFS/OS were assessed in patients with a PFS event who did not receive post-PD therapy (Group 1) and patients with a PFS event who received post-PD therapy plus patients who did not have a PFS event at the final data cutoff (Group 2). Kaplan-Meier methodology was used. A multivariate Cox proportional hazards model for known prognostic variables was generated.
  
  
  
  Baseline characteristics were balanced. In patients with a PFS event who did not receive post-PD therapy (Group 1; n = 225 [24.4% of the intent-to-treat population]), the addition of bevacizumab to radiotherapy/temozolomide resulted in a 3.6-month extension in both median PFS (hazard ratio [HR]: 0.62, P = .0016) and median OS (HR: 0.67, P = .0102). Multivariate analyses supported this OS benefit (HR: 0.66). In the remaining patients (Group 2; n = 696), a 5.2-month PFS extension was observed in bevacizumab-treated patients (HR: 0.61, P < .0001); OS was comparable between the treatment arms (HR: 0.88, P = .1502). No significant differences in safety were observed between the 2 groups.
  
  
  
  This exploratory analysis suggests that the addition of bevacizumab to standard glioblastoma treatment prolongs PFS and OS for patients with PD who receive only one line of therapy.
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.) olivier.chinot@ap-hm.fr.
authors.forename: Olivier L
authors.initials: OL
authors.lastname: Chinot
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishikawa
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).
authors.forename: Warren
authors.initials: W
authors.lastname: Mason
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).
authors.forename: Frank
authors.initials: F
authors.lastname: Saran
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).
authors.forename: Josep
authors.initials: J
authors.lastname: Garcia
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).
authors.forename: Cedric
authors.initials: C
authors.lastname: Revil
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).
authors.forename: Lauren
authors.initials: L
authors.lastname: Abrey
authors.affiliation: Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Saitama Medical University, Saitama, Japan (R.N.); 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, Surrey, UK (F.S.); University of California, Los Angeles, California, USA (T.C.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (J.G., C.R., L.A.); University Medical Center, Heidelberg, Germany (W.W.).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab
keywords: bevacizumab; crossover; glioblastoma; newly diagnosed; overall survival