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Angiogenesis Genotyping and Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib: The ALICE-2 Study

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A Correction to this article was published on 10 November 2020

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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 < 0.0001) and overall survival (OS) (19.0 vs. 13.5 vs. 7.5 months, respectively; p < 0.0001). Furthermore, the presence of the GG genotype of rs12434438 (HIF-1α) seemed able to select a population with a particularly poor outcome, independently from the clinical effect of the two VEGF SNPs (TTP: 2.6 months, HR: 0.54, p = 0.0374; OS: 6.6 months, p = 0.0061, HR: 0.43).

Conclusions

Our findings show that polymorphism analysis of HIF-1α, VEGF, and VEGFR genes may represent a prognostic panel to better identify HCC patients who are more likely to benefit from sorafenib treatment.

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Change history

  • 10 November 2020

    The listing of the author names and affiliations, which previously read.

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Authors and Affiliations

  1. Medical Oncology Unit, Macerata General Hospital, ASUR Marche AV3, Macerata, Italy

    Luca Faloppi, Eva Galizia & Nicola Battelli

  2. Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy

    Luca Faloppi, Marco Puzzoni, Pina Ziranu, Laura Demurtas, Eleonora Lai & Mario Scartozzi

  3. Medical Oncology Unit, IRCSS-IRST, Meldola, Italy

    Andrea Casadei Gardini, Giorgia Marisi & Paola Ulivi

  4. Medical Oncology Unit, IRCCS Giovanni Paolo II Cancer Center, Bari, Italy

    Nicola Silvestris & Cosmo Damiano Gadaleta

  5. Medical Oncology Unit, University of Pisa, Pisa, Italy

    Gianluca Masi, Caterina Vivaldi & Alfredo Falcone

  6. Medical Oncology Unit, San Benedetto del Tronto Hospital, ASUR Marche AV5, San Benedetto del Tronto, Italy

    Maristella Bianconi

  7. International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi “L. Sacco” Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

    Cristian Loretelli

  8. Oncology Department, Polytechnic University of Marche, Ancona, Italy

    Riccardo Giampieri

  9. Medical Oncology Unit, University of Modena, Modena, Italy

    Stefano Cascinu

  10. Oncologia Medica, Azienda Ospedaliera Universitaria Cagliari, Presidio Policlinico Universitario “Duilio Casula”, S.S. 554, Km 4,500 Bivio per Sestu, Monserrato, CA, 09042, Italy

    Mario Scartozzi

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  1. Luca Faloppi
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Correspondence to Mario Scartozzi.

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No external funding was used in the preparation of this article.

Conflict of interest

Luca Faloppi, Marco Puzzoni, Andrea Casadei Gardini, Nicola Silvestris, Gianluca Masi, Giorgia Marisi, Caterina Vivaldi, Cosmo Damiano Gadaleta, Pina Ziranu, Maristella Bianconi, Cristian Loretelli, Laura Demurtas, Eleonora Lai, Riccardo Giampieri, Eva Galizia, Paola Ulivi, Nicola Battelli, Alfredo Falcone, Stefano Cascinu and Mario Scartozzi declare that they have no conflicts of interest that might be relevant to the contents of this article.

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Faloppi, L., Puzzoni, M., Casadei Gardini, A. et al. Angiogenesis Genotyping and Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib: The ALICE-2 Study. Targ Oncol 15, 115–126 (2020). https://doi.org/10.1007/s11523-020-00698-x

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