Sorafenib has demonstrated a significant impact in progression free survival (PFS) in patients with advanced DTC in the DECISION trial. BRAF and RAS mutation status (MS) have not shown prognostic significance on PFS and overall survival (OS) in multivariate model. The aim of this study was to correlate different RNA expression profiles with PFS and OS in a multivariate model.
We previously identified 3 expression profiles, BRAF, RAS and non-BRAF/RAS-like based on RNA-seq analysis (77 million paired-end reads for each sample on HiSeq2000) of 125 tumour samples of patients included in the DECISION trial. RNAseq reads were mapped against the human reference genome (GRCh38) with STAR (v2.5.1b) using ENCODE parameter. We used multivariate Cox proportional models to study the association between clinical variables (sex, age, thyroid cancer histology, Eastern Cooperative Oncology Group performance status), arm of treatment and biomarkers (EP and MS) with PFS and OS.
The clinical variables in each expression profiles are shown in Table. Multivariable analysis indicated that only sorafenib treatment (HR: 0.39, 95% CI 0.23-0.66, p
RNA-seq analysis identifies 3 different expression profiles in DTC: BRAF-like, RAS-like and non-BRAF/RAS-like. BRAF-like EP includes almost all BRAF mutant tumors but also a 45% of tumors with no mutation in BRAF gene. In the multivariate analysis, BRAF-like EP has shown a better prognostic factor for PFS in DTC and for OS in PTC.
Clinical trial identification
Legal entity responsible for the study
Vall d’Hebron Institute of Oncology
Bayer HealthCare Pharmaceuticals, Inc.
C. Peña: Bayer employee. All other authors have declared no conflicts of interest.