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Health-related quality of life outcomes from CABARET: a randomized phase 2 trial of carboplatin and bevacizumab in recurrent glioblastoma

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Abstract

In recurrent glioblastoma, health-related quality of life (HRQL) is a crucial trial endpoint. We examined HRQL outcomes as a secondary endpoint for patients in the CABARET randomized phase 2 trial. 122 patients were randomly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin. We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Brain Cancer Module (QLQ-BN20), together with time to deterioration in HRQL, and the proportion of participants with clinically meaningful improvements in specific disease-related symptoms. At baseline, 117 of 122 randomized patients (96%) attempted questionnaires. Questionnaire participation rates were >90% for patients continuing on treatment, however at the end-of-treatment visit only 72 (64% of eligible participants) returned a form. There were no differences between arms in change scores over the treatment period. Time to ≥10 point deterioration in scores from baseline was also similar between arms. HRQL deterioration occurred largely before progression for the domains tested, but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50% of patients with symptoms at baseline. Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab, with a proportion of patients on both arms experiencing symptomatic benefit. Given the reduced questionnaire completion at end of treatment, time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population. Clinical trials registration number: ACTRN12610000915055.

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Acknowledgements

This trial was conducted under the auspices of the Cooperative Trials Group for Neuro-Oncology (COGNO), coordinated at the NHMRC Clinical Trials Centre, University of Sydney, supported by Roche Products Pty Limited (Australia). Professor King is supported by the Australian Government through Cancer Australia.

Funding

This study was funded by Roche Products, Pty Limited (Australia) with support also from NHMRC Program Grant 1037786 to the NHMRC Clinical Trials Centre, and Cancer Australia Support for Cancer Clinical Trials Grant and CINSW Cooperative Clinical Trials Grant to COGNO.

Author information

Authors and Affiliations

  1. Royal Melbourne Hospital, Parkville, VIC, 3050, Australia

    Kathryn M. Field & Mark A. Rosenthal

  2. Department of Medicine, University of Melbourne, Parkville, VIC, 3050, Australia

    Kathryn M. Field & Mark A. Rosenthal

  3. Psycho-oncology Co-operative Research Group (PoCoG), School of Psychology and Central Clinical School, Sydney Medical School, University of Sydney, Sydney, Australia

    Madeleine T. King

  4. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, 2006, Australia

    John Simes, David Espinoza, Elizabeth H. Barnes & Kate Sawkins

  5. Austin Health, 145 Studley Road, Heidelberg, VIC, 3084, Australia

    Lawrence Cher

  6. Prince of Wales Hospital, Barker Street, Randwick, NSW, 2031, Australia

    Elizabeth Hovey

  7. Department of Medicine, University of New South Wales, Sydney, NSW, Australia

    Elizabeth Hovey

  8. Royal North Shore Hospital, Pacific Highway, St Leonards, NSW, 2065, Australia

    Helen Wheeler

  9. Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia

    Anna K. Nowak

  10. School of Medicine and Pharmacology, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia

    Anna K. Nowak

Authors
  1. Kathryn M. Field
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  2. Madeleine T. King
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  3. John Simes
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  4. David Espinoza
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  5. Elizabeth H. Barnes
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  6. Kate Sawkins
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  7. Mark A. Rosenthal
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  8. Lawrence Cher
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  9. Elizabeth Hovey
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  10. Helen Wheeler
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  11. Anna K. Nowak
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Corresponding author

Correspondence to Kathryn M. Field.

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Conflict of interest

KMF was funded through the University of Melbourne Stella Mary Langford Scholarship and the Royal Melbourne Hospital Research Medal and Watt-Geyer Memorial Research Fund. She has received travel grants from Roche to attend conferences. EJH has had consulting or advisory roles for Bayer, Janssen Oncology, Pfizer, and Roche, and has received travel grants from GlaxoSmithKline and Sanofi. MAR has been on a Roche Advisory Board. LC has received honoraria from and has had consulting or advisory roles for Roche Pharma AG, and has received institutional research funding from Celldex, Lilly, Merck, and Roche. AKN has had consulting or advisory roles for Boehringer Ingelheim and Roche and has received research funding from Boehringer Ingelheim. JS and KS have received institutional research funding from Roche through the Clinical Trials Centre. DE, EB and HW declare no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Research involving animal participants

This article does not contain any studies with animals performed by any of the authors.

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Trial registration

Clinical trials registration number: ACTRN12610000915055.

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Field, K.M., King, M.T., Simes, J. et al. Health-related quality of life outcomes from CABARET: a randomized phase 2 trial of carboplatin and bevacizumab in recurrent glioblastoma. J Neurooncol 133, 623–631 (2017). https://doi.org/10.1007/s11060-017-2479-8

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  • DOI: https://doi.org/10.1007/s11060-017-2479-8

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