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

A partir de données portant sur 858 essais cliniques ayant évalué 12 thérapies ciblées, cette étude analyse l'usage de critères basés sur des biomarqueurs pharmacogénomiques mesurés dans des biopsies pour inclure ou exclure les patients dans ces essais

Résumé en anglais

Purpose: The aim of this study was to describe pharmacogenomics-based inclusion criteria (enrichment) and the 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 the ClinicalTrials.gov database.

Results: We examined information for 12 drugs and 858 trials. Overall, 434 trials (51%) were enriched on the biomarker first mentioned in the label and 145 (17%) were enriched on another biomarker, whereas 270 trials (31%) included all patients. The median proportion of trials corresponding to both the drug’s indication and drug’s target was 35%. Of the 361 trials that 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.

Conclusion: Several drugs have been tested in trials enriched on many different biomarkers. Nonetheless, most targeted therapies have been developed only using biomarker-positive patients; therefore, exclusion of biomarker-negative patients from treatment relies on only preclinical data and on biological understanding of the disease and target.