Angiogenesis Genotyping and Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib: Th
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ORIGINAL RESEARCH ARTICLE
Angiogenesis Genotyping and Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib: The ALICE‑2 Study Luca Faloppi1,2 · Marco Puzzoni2 · Andrea Casadei Gardini3 · Nicola Silvestris4 · Gianluca Masi5 · Giorgia Marisi3 · Caterina Vivaldi5 · Cosmo Damiano Gadaleta4 · Pina Ziranu2 · Maristella Bianconi6 · Cristian Loretelli7 · Laura Demurtas2 · Eleonora Lai2 · Riccardo Giampieri8 · Eva Galizia1 · Paola Ulivi3 · Nicola Battelli1 · Alfredo Falcone5 · Stefano Cascinu9 · Mario Scartozzi2,10
© Springer Nature Switzerland AG 2020
Abstract Background Sorafenib represents one of the therapeutic strongholds for advanced hepatocellular carcinoma (HCC), but unfortunately, predictive factors are lacking. We previously reported that the VEGF single nucleotide polymorphisms (SNPs) rs2010963 and rs4604006 might correlate with clinical outcomes in sorafenib-treated HCC patients. Objective The objective of the ALICE-2 study is to define a prognostic angiogenesis profile to better identify HCC patients who are more likely to benefit from sorafenib treatment. Patients and methods From 2008 to 2015, all consecutive HCC patients receiving sorafenib according to the Italian label were tested for specific HIF-1α, VEGF, and VEGFR SNPs. Results from angiogenesis genotyping were then correlated with clinical outcome parameters. Results Globally, a total of 210 patients were enrolled. At multivariate analysis rs12434438 of HIF1α, rs2010963 of VEGF-A, and rs4604006 of VEGF-C were confirmed as independent predictive factors. At the combined analysis of significant SNPs, the presence of two favourable alleles of rs2010963 and rs4604006 of VEGF compared to only one or to none favourable alleles, was able to identify three separate patients populations with different time-to-progression (TTP) (10.8 vs. 5.6 vs. 3.7 months, respectively; p
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