Evidence map›Paper›PMID 26809751›Full record

Trial reportNeuro-oncology2016

Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy.

Frank Saran, Olivier L Chinot, Roger Henriksson, Warren Mason, Wolfgang Wick, Timothy Cloughesy, Sunita Dhar, Emanuela Pozzi, Josep Garcia, Ryo Nishikawa

Abstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Targeting autophagy for combating chemoresistance and radioresistance in glioblastoma.Apoptosis : an international journal on programmed cell death · 2018
    Pooled it
  5. Article
  6. NSUN7-mediated mJournal of translational medicine · 2025
    Article
  7. DUSP8 as a regulator of glioblastoma stem-like cell contribution to tumor vascularization.Journal of experimental & clinical cancer research : CR · 2025
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Glioblastoma Therapy: Past, Present and Future.International journal of molecular sciences · 2024
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Proteomic Distributions in CD34+ Microvascular Niche Patterns of Glioblastoma.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Frank SaranThe 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.).
Olivier L ChinotThe 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.).
Roger HenrikssonThe 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.).
Warren MasonThe 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.).
Wolfgang WickThe 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.).
Timothy CloughesyThe 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.).
Sunita DharThe 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.).
Emanuela PozziThe 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.).
Josep GarciaThe 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.).
Ryo NishikawaThe 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.).

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 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.

methodsEligible 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.

resultsBevacizumab-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).

conclusionThe 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.

Indexed as

ChemoradiotherapyAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedBevacizumabBrain NeoplasmsDacarbazineDisease ProgressionFemaleGlioblastomaHumansMaleMiddle AgedTemozolomideTreatment OutcomeAntibodies, Monoclonal, HumanizedBevacizumabDacarbazineTemozolomideadverse eventsAVAgliobevacizumabglioblastomasafety

Identifiers

PMID26809751
PMCPMC4896538

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.