The search for surrogacy in patient derived xenograft mouse trials: glass is less than half full
Mistry, H.
Show abstract
Despite the efforts of many within the drug development and clinical community surrogate biomarkers for patient survival have remained elusive in Oncology. This failure in part is attributable to there being a paucity of clinical trials showing a treatment effect on patient survival. Given this issue an alternative system to explore the surrogacy potential of biomarkers are large preclinical xenograft studies i.e. panel of patient derived xenografts or mouse clinical trials. In this study we explored the surrogacy potential of tumour burden biomarkers, current size of tumour and how its changed, preclinically in a large patient derived xenograft database which contains a diverse number of drugs/treatments (n=61) and xenografts (n=245). We found that of the possible 1830 two-arm mouse trials, 1103 showed a treatment effect on the preclinical end-point, disease progression, (p<0.05). Of these only in 30% did tumour burden markers fully capture the treatment effect on disease progression times i.e. satisfied a key condition for surrogacy. These results highlight that preclinically it is very challenging to find a surrogate marker based purely on measures of tumour burden.
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