title: Health-Related Quality of Life in a Randomized Phase III Study of Bevacizumab, Temozolomide, and Radiotherapy in Newly Diagnosed Glioblastoma.
abstract: OBJECTIVE
  As glioblastoma progresses, patients experience a decline in health-related quality of life (HRQoL). Delaying this decline is an important treatment goal. In newly diagnosed glioblastoma, progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide (RT/TMZ) versus placebo plus RT/TMZ (phase III AVAglio study; hazard ratio, 0.64; 95% CI, 0.55 to 0.74; P < .001). To ensure that addition of bevacizumab to standard-of-care therapy was not associated with HRQoL detriment, HRQoL assessment was a secondary objective.
  
  
  METHODS
  Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BN20 at each tumor assessment (Appendix Table A1, online only). Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated (stable: < 10-point change; clinically relevant deterioration/improvement: ≥ 10-point change). Deterioration-free survival was the time to deterioration/progression/death; time to deterioration was the time to deterioration/death.
  
  
  RESULTS
  Most evaluable patients who had not progressed (> 74%) completed all HRQoL assessments for at least 1 year of treatment, and almost all completed at least one HRQoL assessment at baseline (98.3% and 97.6%, bevacizumab and placebo arms, respectively). Mean changes from baseline did not reach a clinically relevant difference between arms for most items. HRQoL declined at progression in both arms. The addition of bevacizumab to RT/TMZ resulted in statistically longer (P < .001) deterioration-free survival across all items. Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm (v bevacizumab) for any HRQoL item.
  
  
  CONCLUSIONS
  The addition of bevacizumab to standard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period.
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France. m.taphoorn@mchaaglanden.nl.
authors.forename: Martin J B
authors.initials: MJ
authors.lastname: Taphoorn
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bottomley
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Warren P
authors.initials: WP
authors.lastname: Mason
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Saran
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishikawa
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Hilton
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Theodore-Oklota
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Arliene
authors.initials: A
authors.lastname: Ravelo
authors.affiliation: Martin J.B. Taphoorn, Medical Center Haaglanden, the Hague, and VU University Medical Center, Amsterdam, the Netherlands; Roger Henriksson, Cancer Center Stockholm Gotland, Karolinska, Stockholm, and Umeå University, Umeå, Sweden; Andrew Bottomley, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Timothy Cloughesy, University of California, Los Angeles, Los Angeles; Christina Theodore-Oklota and Arliene Ravelo, Genentech, South San Francisco, CA; Wolfgang Wick, University Hospital of Heidelberg, Heidelberg, Germany; Warren Mason, Princess Margaret Hospital, Toronto, Ontario, Canada; Frank Saran, The Royal Marsden National Health Service Foundation Trust, Surrey, United Kingdom; Ryo Nishikawa, Saitama Medical University, Saitama, Japan; Magalie Hilton, F. Hoffmann-La Roche, Basel, Switzerland; Olivier L. Chinot, Service de Neuro-Oncologie, Aix-Marseille University, Assistance Publique- Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Marseille, France.
authors.forename: Olivier L
authors.initials: OL
authors.lastname: Chinot
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000628:therapy*; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018906:Antineoplastic Agents, Alkylating; D010919:Placebos; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide