Angiogenesis polymorphisms profile in the prediction of clinical outcome of advanced HCC patients receiving sorafenib: Combined analysis of VEGF and HIF-1α—Final results of the ALICE-2 study.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


Poster Board Number: 
Poster Session B Board #E4
J Clin Oncol 34, 2016 (suppl 4S; abstr 280)
Luca Faloppi, Andrea Casadei Gardini, Gianluca Masi, Nicola Silvestris, Cristian Loretelli, Paola Ulivi, Caterina Vivaldi, Maristella Bianconi, Riccardo Giampieri, Alessandro Bittoni, Kalliopi Andrikou, Michela Del Prete, Mario Scartozzi, Stefano Cascinu; Department of Medical Oncology, A.O.U. United Hospital, Polytechnic University of the Marche Region, Ancona, Italy; IRST-IRCCS, Meldola, Italy; U.O. Oncologia Medica II, Azienda Ospedaliero-Universitaria Pisana Istituto Toscano Tumori, Pisa, Italy; Medical Oncology Unit, Cancer Institute Giovanni Paolo II, Bari, Italy; Centro Regionale di Genetica Oncologica, A.O. Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy; Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; Universita Di Pisa, Pisa, Italy; Department of Medical Oncology, A.O. Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy; Clinica di Oncologia Medica, Università Politecnica delle Marche, Ancona, Italy; Scuola di Specializzazione in Oncologia Medica UNIVPM, Ancona, Italy; University Hospital of Cagliari, Cagliari, Italy; Clinica di Oncologia Medica, Università Politecnica delle Marche, A.O. Ospedali Riuniti, Ancona, Italy

Abstract Disclosures


Background: HIF-1α plays a crucial role in tumour angiogenesis triggering the transcription of several genes including VEGF. The overexpression of HIF-1α in HCC is associated with tumour angiogenesis, invasion, metastasis, treatment resistance and poor prognosis. The therapeutic stronghold of advanced HCC is the TKI sorafenib. In our previous report (ALICE-1 study) SNPs rs2010963 and rs4604006 of VEGF have been shown to predict clinical outcome in HCC patients treated with sorafenib. Methods: 210 patients from a multicentre database were eligible for our analysis. Tumour samples were tested for 8 HIF-1α SNPs. Patients PFS and OS were analysed. Results: At univariate analysis CC > AA+AC of rs1951795, TT > CC+CT of rs10873142, AA+AG > GG of rs12434438 SNPs of HIF-1α were statistically significant for PFS and OS. The extended analysis of VEGF and VEGFR SNPs confirms the results of ALICE-1 study. At multivariate analysis rs12434438 of HIF-1α, rs2010963 of VEGF-A and rs4604006 of VEGF-C have been confirmed as independent factors. At the combined analysis of significant SNPs the presence of 2 favourable alleles of rs2010963 and rs4604006 of VEGF compared to only 1 or to none favourable alleles, identifies three populations with different PFS (respectively: 10.8 vs. 5.6 vs. 3.7 months, p < 0,0001) and OS (respectively: 19.0 vs. 13.5 vs. 7.5 months; p < 0,0001). Furthermore the presence of GG genotype of rs12434438 (HIF-1α) select a population with a particularly poor outcome independently from the clinical effect of the two VEGF SNPs (PFS: 2.6 months, p < 0,0001; OS: 6.6 months, p < 0,0001). Conclusions: This investigation on HIF-1α SNPs, following our previous discoveries on VEGF and VEGFR, may represent a clinical tool to identify patients with favourable response to sorafenib. In the presence of a favourable genotyping, clinicians would administer sorafenib as soon as clinically indicated, instead of delaying it with other treatments. Conversely patients with unfavourable genotyping may not be optimal candidates for sorafenib. These patients should be preferably included in clinical trials exploring new treatment options.