432PD - Prognostic impact of RNA expression profile (EP) in the phase III DECISION trial for patients with advanced radioactive-iodine refractory different...

Date 11 September 2017
Event ESMO 2017 Congress
Session Endocrine and neuroendocrine tumours
Topics Thyroid Cancer
Endocrine Cancers
Translational Research
Presenter Ignacio Matos
Citation Annals of Oncology (2017) 28 (suppl_5): v142-v157. 10.1093/annonc/mdx368
Authors I. Matos1, F. Mancuso2, C. Iglesias3, P. Nuciforo4, C. Zafón5, H.G. Palmer6, Z. Ogbah2, L. Muños2, G. Villacampa Javierre7, C. Peña8, M.S. Brose9, M. Schlumberger10, A. Vivancos2, J. Capdevila1
  • 1Oncology, Vall d`Hebron Institute of Oncology (VHIO)-Cellex Center, 08035 - Barcelona/ES
  • 2Cancer Genomics Group, Vall d´Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 3Pathology, Valle d´Hebron University Hospital, 08035 - Barcelona/ES
  • 4Molecular Oncology Group, Vall d´Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 5Endocrinology, Valle d´Hebron University Hospital, 08035 - Barcelona/ES
  • 6Stem Cells And Cancer Group, Vall d`Hebron Institute of Oncology (VHIO)-Cellex Center, 08035 - Barcelona/ES
  • 7Oncology Data Science (odyssey) Group, Vall d'Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 8Biomarker Strategy, Bayer HealthCare Pharmaceuticals, 07981 - Whippany/US
  • 9Medical Oncology, University of Pennsylvania- CRB, 19104 - Philadelphia/US
  • 10Oncology, Gustave Roussy Institut de Cancérologie, 94805 - Villejuif/FR

Abstract

Background

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.

Methods

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.

Results

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 

Conclusions

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

Funding

Bayer HealthCare Pharmaceuticals, Inc.

Disclosure

C. Peña: Bayer employee. All other authors have declared no conflicts of interest.