Fibroblast Growth Factor Receptors and Ligands in Context of Bevacizumab Response in Ovarian Carcinoma: An Exploratory Analysis of AGO-OVAR 11/ICON-7

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Sabine Heublein - , Universitätsklinikum Heidelberg (Autor:in)
  • Jacobus Pfisterer - , Gynecologic Oncology Center (Autor:in)
  • Andreas du Bois - , KEM | Evang. Kliniken Essen-Mitte gGmbH (Autor:in)
  • Michael Anglesio M - , University of British Columbia (Autor:in)
  • Behnaz Aminossadati - , Philipps-Universität Marburg (Autor:in)
  • Irfan Bhatti - , Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg (Autor:in)
  • Jalid Sehouli - , Steinbeis University Berlin (Autor:in)
  • Pauline Wimberger - , Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (Autor:in)
  • Fabienne Schochter - , Universitätsklinikum Ulm (Autor:in)
  • Felix Hilpert - , Krankenhaus Jerusalem (Autor:in)
  • Peter Hillemanns - , Medizinische Hochschule Hannover (MHH) (Autor:in)
  • Matthias Kalder - , Philipps-Universität Marburg (Autor:in)
  • Willibald Schroeder - , Gynaekologicum Bremen (Autor:in)
  • Sven Mahner - , University Hospital Olomouc (Autor:in)
  • Alexander Burges - , University Hospital Olomouc (Autor:in)
  • Ulrich Canzler - , Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (Autor:in)
  • Martina Gropp-Meier - , Oberschwabenklinik Ravensburg (Autor:in)
  • Christian Jackisch - , Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (Autor:in)
  • Philipp Harter P - , KEM | Evang. Kliniken Essen-Mitte gGmbH (Autor:in)
  • Stefan Kommoss - , Universitätsklinikum Tübingen (Autor:in)
  • Frederik Marmé - , Universität Heidelberg (Autor:in)

Abstract

With more novel drugs being approved for the treatment of ovarian carcinoma (OC), the question remains to what extent patients benefit from anti-angiogenic treatment with bevacizumab, either in combination with poly (ADP-ribose) polymerase (PAPR) inhibitors or as single-agent maintenance. As fibroblast growth factor receptors and their ligands (FGFRs/FGFs) are key players in angiogenic signaling and have been linked to resistance to several drugs, we investigated the prognostic or predictive potential of FGFs/FGFRs signaling in the context of bevacizumab treatment within the prospective phase III AGO-OVAR 11/ICON-7 study. FGFR1, FGFR2, FGFR3, FGFR4, FGF1, and FGF19 gene expression was determined in 380 OC tumor samples collected from German centers in the multicenter phase III AGO-OVAR11 trial/ICON-7 trial. All patients received carboplatin and paclitaxel given every three weeks for six cycles and were randomized to bevacizumab. Expression of FGFR1, FGFR2, FGF1, and FGF19 was associated with progression-free survival (PFS) in both uni- and multivariate (FGFR1: HR=1.6, p<0.001; FGFR2: HR=1.6, p=0.002; FGF1: HR=2.3, p<0.001; FGF19: HR=0.7; p=0.007) analysis. A signature built by FGFR1, FGFR4, and FGF19 defined a subgroup (n=62) of patients that derived the greatest bevacizumab-associated improvement of PFS (HR=0.3, p=0.004). In this exploratory analysis of a prospective randomized phase III trial, we provide evidence that expression of FGFRs/FGFs might have independent prognostic value. An FGFR/FGF-based gene signature identified in our study appears to predict long-term benefit from bevacizumab. This observation is hypothesis-generating and requires validation on independent cohorts.

Details

OriginalspracheEnglisch
Aufsatznummer100321
Seitenumfang9
FachzeitschriftLaboratory investigation
Jahrgang104
Ausgabenummer4
Frühes Online-Datum26 Dez. 2023
PublikationsstatusVeröffentlicht - Apr. 2024
Peer-Review-StatusJa

Externe IDs

Scopus 85188548378

Schlagworte

Schlagwörter

  • Bevacizumab/pharmacology, Carcinoma, Female, Fibroblast Growth Factor 1, Fibroblast Growth Factors, Humans, Ovarian Neoplasms/drug therapy, Prospective Studies

Bibliotheksschlagworte