title: Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy.
abstract: The proposed use of bevacizumab with radiotherapy/temozolomide for newly diagnosed glioblastoma raised potential safety concerns. Bevacizumab has been linked with stroke, bleeding events, and wound-healing complications in other tumor types; these events are of particular concern for glioblastoma (highly vascular tumors that are usually resected). Published data on the interaction of bevacizumab with radiotherapy/temozolomide are also limited. We report safety data from a phase III randomized trial (Avastin in Glioblastoma), focusing on these considerations.
  
  
  
  Eligible patients received: radiotherapy and temozolomide plus bevacizumab/placebo, 6 cycles; a 4-week treatment break; temozolomide plus bevacizumab/placebo, 6 cycles; and bevacizumab/placebo until progression. Data on adverse events (AEs) were collected throughout.
  
  
  
  Bevacizumab-treated patients (n = 461) had a longer median safety follow-up time (12.3 vs 8.5 mo), and a higher proportion completed 6 cycles of maintenance temozolomide (64.6% vs 36.9%) versus placebo (n = 450). The incidences of relevant AEs (bevacizumab vs placebo, respectively) were: arterial thromboembolic events (5.9% vs 1.6%); cerebral hemorrhage (3.3% vs 2.0%); wound-healing complications (6.9% vs 4.7%); thrombocytopenia (34.1% vs 27.3%); radiotherapy-associated skin injury (8.2% vs 9.3%); alopecia (39.0% vs 36.0%); gastrointestinal perforation (including gastrointestinal abscesses and fistulae, 1.7% vs 0.4%); and radiotherapy-associated injury (0.4% vs 0.0%). Overall, 15.8% and 23.8% of bevacizumab- and placebo-treated patients had surgery (including biopsy) after progression. Within 30 days of postprogression surgery, AE incidence was 10.9% (bevacizumab) and 23.4% (placebo).
  
  
  
  The safety profile was consistent with that expected from radiotherapy/temozolomide plus bevacizumab. The increased AE incidence with bevacizumab did not impact patients' ability to receive standard-of-care treatment or to undergo further surgery.
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Frank
authors.initials: F
authors.lastname: Saran
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Olivier L
authors.initials: OL
authors.lastname: Chinot
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Warren
authors.initials: W
authors.lastname: Mason
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Sunita
authors.initials: S
authors.lastname: Dhar
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pozzi
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Josep
authors.initials: J
authors.lastname: Garcia
authors.affiliation: The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK (F.S.); Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France (O.L.C.); Regional Cancer Center, Stockholm-Gotland, Karolinska University Hospital, Stockholm, Sweden (R.H.); Department of Radiation Sciences and Oncology, Umeå University, Förvaltningshuset, Universitetstorget, Umeå, Sweden (R.H.); Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada (W.M.); University Medical Center and German Cancer Research Center, Heidelberg, Germany (W.W.); University of California, Los Angeles, California, USA (T.C.); Genentech Inc., South San Francisco, California, USA (S.D.); F. Hoffmann-La Roche Ltd, Basel, Switzerland (E.P., J.G.); Saitama Medical University, Saitama, Japan (R.N.).
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishikawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide
keywords: AVAglio; adverse events; bevacizumab; glioblastoma; safety
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