Upfront bevacizumab may extend survival for glioblastoma patients who do not receive second-line therapy: an exploratory analysis of AVAglio

Olivier L Chinot; Ryo Nishikawa; Warren Mason; Roger Henriksson; Frank Saran; Timothy Cloughesy; Josep Garcia; Cedric Revil; Lauren Abrey; Wolfgang Wick

doi:10.1093/neuonc/now046

Upfront bevacizumab may extend survival for glioblastoma patients who do not receive second-line therapy: an exploratory analysis of AVAglio

Neuro Oncol. 2016 Sep;18(9):1313-8. doi: 10.1093/neuonc/now046. Epub 2016 Mar 22.

Authors

Affiliations

¹ 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.
² 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.).

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00943826.

Keywords: bevacizumab; crossover; glioblastoma; newly diagnosed; overall survival.

Publication types

Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Angiogenesis Inhibitors / therapeutic use*
Bevacizumab / therapeutic use*
Brain Neoplasms / drug therapy
Brain Neoplasms / mortality*
Brain Neoplasms / pathology
Double-Blind Method
Female
Follow-Up Studies
Glioblastoma / drug therapy
Glioblastoma / mortality*
Glioblastoma / pathology
Humans
Male
Middle Aged
Neoplasm Staging
Prognosis
Salvage Therapy*
Survival Rate
Time Factors
Young Adult

Substances

Angiogenesis Inhibitors
Bevacizumab

Associated data

ClinicalTrials.gov/NCT00943826