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

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.