Developing an objective marker to optimize patient selection and predict survival benefit in early‐phase cancer trials. Issue 2 (8th October 2013)

• Record Type: Journal Article
• Authors: Stavraka, Chara; Pinato, David J.; Turnbull, Samantha J.; Flynn, Michael J.; Forster, Martin D.; O'Cathail, Sean M.; Babar, Sayed; Seckl, Michael J.; Kristeleit, Rebecca S.; Blagden, Sarah P.
• Is Part Of: Cancer. Volume 120:Issue 2(2014)
• Page Start: 262
• Page End: 270
• Publication Date: 2013-10-08
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28381
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28381-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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.</p> </sec> <sec id="cncr28381-sec-0002" sec-type="section"> <title>METHODS</title> <p>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.</p> </sec> <sec id="cncr28381-sec-0003" sec-type="section"> <title>RESULTS</title> <p>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, <italic>P</italic> < .001), PFS (HR = 2.8, <italic>P</italic> = .01), and 90DM (OR = 9.0, <italic>P</italic> < .001). HS was a more accurate multivariate predictor of OS (HR = 6.4, <italic>P</italic> < .001, C‐index = 0.72), PFS (HR = 2.7, <italic>P</italic> = .03), and 90DM (area under the ROC curve 0.703) compared with other scores. Worsening of the HS during treatment predicted for shorter OS (<italic>P</italic> < .001). HS retained prognostic and predictive ability following external validation.</p> </sec> <sec id="cncr28381-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>HS is a simple, validated index to optimize patient selection and predict survival benefit from phase 1 oncology treatments. Prospective validation is ongoing. <bold><italic>Cancer</italic> 2014;120:262–270.</bold> © <italic>2013 American Cancer Society</italic>.</p> </sec> </abstract>