Evaluation of efficacy and safety markers in a phase II study of metastatic colorectal cancer treated with aflibercept in the first-line setting

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Diether Lambrechts - , Flanders Institute for Biotechnology (VIB), KU Leuven (Autor:in)
  • Bernard Thienpont - , Flanders Institute for Biotechnology (VIB), KU Leuven (Autor:in)
  • Vincent Thuillier - , Sanofi-Aventis (Autor:in)
  • Xavier Sagaert - , KU Leuven (Autor:in)
  • Matthieu Moisse - , Flanders Institute for Biotechnology (VIB), KU Leuven (Autor:in)
  • Gilian Peuteman - , Flanders Institute for Biotechnology (VIB), KU Leuven (Autor:in)
  • Carles Pericay - , Autonomous University of Barcelona (Autor:in)
  • Gunnar Folprecht - , Medizinische Klinik und Poliklinik I, Universitäts KrebsCentrum Dresden, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • John Zalcberg - , Monash University (Autor:in)
  • Chiara Zilocchi - , Sanofi-Aventis (Autor:in)
  • Emmanuelle Margherini - , Sanofi-Aventis (Autor:in)
  • Marielle Chiron - , Sanofi-Aventis (Autor:in)
  • Eric Van Cutsem - , KU Leuven (Autor:in)

Abstract

Background:Aflibercept (ziv-aflibercept) is an anti-angiogenic agent recently approved in combination with FOLFIRI for the treatment of metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. Despite heterogeneity in response to aflibercept, no biomarkers for efficacy or adverse effects have been identified. Here we present biomarker data from the randomised phase II AFFIRM trial assessing aflibercept in combination with mFOLFOX6 first line in mCRC.Methods:Ninety-six somatic mutations in key oncogenic drivers of mCRC and 133 common single-nucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF) pathway genes were analysed, and 27 plasma markers measured at baseline, during and after treatment. We assessed correlations of these three classes of biomarkers with progression-free survival (PFS) and adverse events (AEs).Results:Somatic mutations identified in KRAS, BRAF, NRAS, PIK3CA and PIK3R1 did not significantly correlate with PFS (multiple testing-adjusted false discovery rate (FDR) or multiple testing-adjusted FDR>0.3). None of the individual SNPs correlated with PFS (multiple testing-adjusted FDR>0.22), but at the gene level variability in VEGFB significantly correlated with PFS (multiple testing-adjusted FDR=0.0423). Although none of the plasma markers measured at baseline significantly correlated with PFS, high levels of circulating IL8 at baseline together with increased levels of IL8 during treatment were significantly associated with reduced PFS (multiple testing-adjusted FDR=0.0478). No association was found between biomarkers and AEs.Conclusions:This represents the first biomarker study in mCRC treated with aflibercept. High IL8 plasma levels at baseline and subsequent increases in IL8 were associated with worse PFS, suggesting that IL8 may act as a potentially predictive biomarker of aflibercept treatment outcome.

Details

OriginalspracheEnglisch
Seiten (von - bis)1027-1034
Seitenumfang8
FachzeitschriftBritish journal of cancer
Jahrgang113
Ausgabenummer7
PublikationsstatusVeröffentlicht - 29 Sept. 2015
Peer-Review-StatusJa

Externe IDs

PubMed 26355232
ORCID /0000-0002-9321-9911/work/163766375

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • anti-angiogenesis; aflibercept; metastatic colorectal cancer; predictive marker; KRAS mutation status; IL8