Pharmacogenomic biomarkers as inclusion criteria in clinical trials of oncology-targeted drugs: a mapping of ClinicalTrials.gov

Alexandre Vivot (1) , Jacques Li , Jean-David Zeitoun , Samia Mourah , Perrine Crequit , Philippe Ravaud , Raphaël Porcher

1 Centre d'épidémiologie clinique

Purpose: To describe pharmacogenomics-based inclusion criteria (enrichment) and main characteristics of clinical trials involving oncology targeted therapies. Methods: Clinical trials of oncology targeted therapies approved after 2005 with pharmacogenomic testing required or recommended in their label were retrieved from a mapping of clinicaltrials.gov database. Results: We included 12 drugs and 858 trials. Overall, 434 trials (51%) were enriched on the biomarker first mentioned in the label and 145 (17%) on another biomarker whereas 270 (31%) trials included all patients. The median proportion of trials corresponding to both the drug's indication and drug's target was 35%. Among the 361 trials which tested drugs in another disease than the first one in the label, 219 (61%) were without enrichment and 87 (24%) were actually enriched but on another biomarker than the first one in the label. Conclusions: Several drugs have been tested in trials enriched on many different biomarkers. Nonetheless, most of targeted therapies have been developed only in biomarker-positive patients and, therefore, exclusion of biomarker-negative patients from treatment relies on only pre-clinical data and on biological understanding of the disease and target.

Mots clés: clinical trials; biomarkers; pharmacogenomics; food and druf administration; personalized medicine

Domaines: Sciences du Vivant [q-bio]

Alexandre Vivot, Jacques Li, Jean-David Zeitoun, Samia Mourah, Perrine Crequit, et al.. Pharmacogenomic biomarkers as inclusion criteria in clinical trials of oncology-targeted drugs: a mapping of ClinicalTrials.gov. Genetics in Medicine, 2015, ⟨10.1038/gim.2015.165⟩. ⟨hal-01867573⟩