Developing an objective marker to optimize patient selection and predict survival benefit in early-phase cancer trials

Authors

  • Chara Stavraka MD, MRes,

    1. Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
    Search for more papers by this author
    • We acknowledge Dr. Bernard North, part funded by the Imperial Experimental Cancer Medicine Centre (ECMC) grant from Cancer Research UK (CR-UK) and the UK Department of Health (DoH), for his statistical support as well as Farah Williams for her contribution to retrieving patient records.

  • David J. Pinato MD, MRes, PhD,

    1. Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
    Search for more papers by this author
    • We acknowledge Dr. Bernard North, part funded by the Imperial Experimental Cancer Medicine Centre (ECMC) grant from Cancer Research UK (CR-UK) and the UK Department of Health (DoH), for his statistical support as well as Farah Williams for her contribution to retrieving patient records.

  • Samantha J. Turnbull MBBS,

    1. University College London Clinical Research Facility, University College London Hospital, London, United Kingdom
    Search for more papers by this author
  • Michael J. Flynn MBBS,

    1. University College London Clinical Research Facility, University College London Hospital, London, United Kingdom
    Search for more papers by this author
  • Martin D. Forster MRCP, PhD,

    1. University College London Cancer Institute, University College London, London, United Kingdom
    Search for more papers by this author
  • Sean M. O'Cathail MBBS,

    1. Department of Medical Oncology, Imperial College London, Hammersmith Campus, London, United Kingdom
    Search for more papers by this author
  • Sayed Babar DMRD,

    1. Imaging Department, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
    Search for more papers by this author
  • Michael J. Seckl MRCP, PhD,

    1. Department of Medical Oncology, Imperial College London, Hammersmith Campus, London, United Kingdom
    Search for more papers by this author
  • Rebecca S. Kristeleit MRCP, PhD,

    1. University College London Cancer Institute, University College London, London, United Kingdom
    Search for more papers by this author
  • Sarah P. Blagden MRCP, PhD

    Corresponding author
    1. Department of Medical Oncology, Imperial College London, Hammersmith Campus, London, United Kingdom
    • Corresponding author: Sarah P. Blagden, PhD, Senior Lecturer and Consultant Medical Oncologist, Department of Medical Oncology, Imperial College London, Hammersmith Campus, Du Cane Road, W120HS London, United Kingdom; Fax: (011) 44 (0) 208 3833054; s.blagden@imperial.ac.uk

    Search for more papers by this author

  • The first 2 authors contributed equally to this work and should be considered joint first authors.

Abstract

BACKGROUND

Several prognostic indices have been devised to optimize patient selection for phase 1 oncology trials with no consensus as to the optimal score and none qualifying as a marker of treatment response.

METHODS

Multivariate predictors of overall survival (OS) were tested on 118 referred patients to develop the Hammersmith Score (HS). The score's ability to predict OS, progression-free survival (PFS), and 90-day mortality (90DM) was compared with other prognostic indices. Changes in HS were recalculated during treatment.

RESULTS

Albumin < 35 g/L, lactate dehydrogenase > 450 U/L, and sodium < 135 mmol/L emerged as independent prognostic factors. These were used with equal weighting to devise the HS, a compound prognostic index ranging from 0 to 3. High (HS = 2-3) score predicted worse OS (hazard ratio [HR] = 6.5, P < .001), PFS (HR = 2.8, P = .01), and 90DM (OR = 9.0, P < .001). HS was a more accurate multivariate predictor of OS (HR = 6.4, P < .001, C-index = 0.72), PFS (HR = 2.7, P = .03), and 90DM (area under the ROC curve 0.703) compared with other scores. Worsening of the HS during treatment predicted for shorter OS (P < .001). HS retained prognostic and predictive ability following external validation.

CONCLUSIONS

HS is a simple, validated index to optimize patient selection and predict survival benefit from phase 1 oncology treatments. Prospective validation is ongoing. Cancer 2014;120:262–270. © 2013 American Cancer Society.

Ancillary