Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer
Mené à partir d'échantillons plasmatiques prélevés sur 89 patients atteints d'un cancer de la prostate résistant à la castration, cette étude évalue l'association entre les niveaux de 14 microARNs, mesurés par PCR en temps réel, et la survie globale ou la réponse à une chimiothérapie par docétaxel
Background : Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings.
Methods : Using real-time PCR, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients.
Results : The microRNAs were not associated with docetaxel response in the Phase 2 cohort. Higher baseline levels of six microRNAs, predominantly of the miR-200 family, were confirmed to be associated with shorter overall survival. A microRNA signature comprising these six microRNAs predicted high-risk patients in the Phase 2 cohort with a hazard ratio of 4.12 (95% CI 2.20–7.70, P=0.000001). The signature was an independent predictor in multivariable analysis with clinicopathological factors.
Conclusions : The association of circulating microRNAs with overall survival suggests their involvement in CRPC progression.
British Journal of Cancer , résumé, 2016