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Sorafenib and Clinical Patterns of Resistance in Hepatocellular Carcinoma

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Resistance to Molecular Therapies for Hepatocellular Carcinoma

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 13))

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Abstract

Sorafenib is the first-line systemic treatment in hepatocellular carcinoma (HCC). The benefits of sorafenib in HCC show an improvement in overall survival and delay of radiologic tumor progression. These benefits were demonstrated in the absence of a high rate of overall response and the magnitude of this improvement varies considerably from patient to patient. Several hypotheses have tried to address the reason for this variability, giving birth to the emerging field of sorafenib resistance. The aim of this chapter is to discuss the clinical evolutionary events such as early dermatologic adverse events, pattern of progression or serum biomarkers modification that have an impact both on the patient’s outcome as well as in the patient’s management. The pattern of progression classifies patients in four different groups: (1) intra-hepatic (2) extra-hepatic increase in tumor size (3) new intra-hepatic lesion and (4) new extra-hepatic lesion and it is correlated with the post-progression overall survival. Hence, careful evaluation of patients characteristics and their evolutionary events during sorafenib treatment are key to identify the best candidates to continue on sorafenib, those who should receive regorafenib as second-line treatment, second-line trials or best supportive care. In addition, the design of second- and third-line clinical trials should consider all the components discussed in this chapter.

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Abbreviations

AE:

Adverse event

AFP:

Alpha-fetoprotein

ANGPT2:

Angiopoyetin-2

BCLC:

Barcelona Clinic Liver Cancer

DAE60:

DAEs within the first 60 days requiring sorafenib dose modification

DAEs:

Dermatologic adverse events

EASL:

European Association for the Study of Liver Diseases

HCC:

Hepatocellular carcinoma

HGF:

Hepatocyte growth factor

PDGFR-β:

Platelet-derived growth factor receptor β

PPS:

Post-progression survival

TTP:

Time to progression

VEGFRs:

Vascular endothelial growth factor receptor

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Conflict of Interest

Maria Reig = Advisory boards, conferences, travel grants from Bayer.

Author information

Authors and Affiliations

  1. Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain

    Maria Reig, Álvaro Díaz-Gonzalez & Andrea Ribeiro

  2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), c/Villarroel, 170. Escala 11, 4ª planta, 08036, Barcelona, Spain

    Maria Reig, Álvaro Díaz-Gonzalez & Andrea Ribeiro

  3. Department of Radiology, BCLC Group, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain

    Anna Darnell

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  1. Maria Reig
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Correspondence to Maria Reig .

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  1. Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, Graduate School of Biomedical Sciences, New York, New York, USA

    Augusto Villanueva

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Reig, M., Díaz-Gonzalez, Á., Ribeiro, A., Darnell, A. (2017). Sorafenib and Clinical Patterns of Resistance in Hepatocellular Carcinoma. In: Villanueva, A. (eds) Resistance to Molecular Therapies for Hepatocellular Carcinoma. Resistance to Targeted Anti-Cancer Therapeutics, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-56197-4_7

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