Predicting response to bevacizumab in ovarian cancer: a panel of potential biomarkers informing treatment selection
Menée sur des échantillons sériques prélevés sur 10 patientes atteintes d'un cancer épithélial de l'ovaire ayant été traité à l'aide de bévacizumab, puis validée sur deux cohortes complémentaires de 92 et 115 patientes, cette étude identifie une signature, basée sur quatre biomarqueurs, en association avec la réponse thérapeutique
Purpose: The aim of this study was to identify and validate novel predictive and/or prognostic serum proteomic biomarkers in patients with epithelial ovarian cancer (EOC) treated as part of the phase III international ICON7 clinical trial.
Experimental design: ICON7 demonstrated a modest but statistically significant benefit in progression-free survival with the addition of bevacizumab to standard chemotherapy. Serum samples from 10 patients who received bevacizumab (5 responders, 5 non-responders) were analysed by mass spectrometry to identify candidate biomarkers. Initial validation by immunoassay across both arms of the trial was undertaken in an independent cohort of 92 patients, followed by a second independent cohort of 115 patients.
Results: Three candidate biomarkers were identified, mesothelin, fms-like tyrosine kinase-4 (FLT4) and 1-acid glycoprotein (AGP). Each showed evidence of independent prognostic potential when adjusting for high risk status in initial (p<0.02) and combined (p<0.01) validation cohorts. In cohort I individual biomarkers were not predictive of bevacizumab benefit; however, when combined with CA-125, a signature was developed that was predictive of bevacizumab response and discriminated benefit attributable to bevacizumab better than clinical characteristics. The signature showed weaker evidence of predictive ability in validation cohort II, but was still strongly predictive considering all samples (p=0.001), with an improvement in median PFS of 5.5 months in signature-positive patients in the experimental arm compared to standard arm.
Conclusions: This study demonstrates a discriminatory four protein signature as potentially identifying those patients with EOC more likely to benefit from bevacizumab. These results require validation in further patient cohorts.
Clinical Cancer Research , résumé, 2013