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Ramucirumab as a second line therapy for advanced HCC: a significant achievement or a wasted opportunity for

Giandomenico Roviello1, Navid Sohbani2, Roberto Petrioli3

  • 1Department of Health Sciences, University of Florence, viale Pieraccini, 6, 50139, Florence, Italy. giandomenicoroviello@hotmail.it.

Investigational New Drugs
|March 18, 2019
PubMed

Insights

Ramucirumab shows survival benefits as a second-line treatment for advanced hepatocellular carcinoma (HCC) in patients with high AFP levels. Further research is needed to identify predictive biomarkers for personalized HCC therapy.

Area of Science:

  • Hepatocellular carcinoma (HCC) research
  • Cancer angiogenesis pathways
  • Vascular endothelial growth factor (VEGF) signaling

Background:

  • Second-line treatment options for advanced HCC are limited, with a recent focus on therapies demonstrating survival benefits.
  • Predictive biomarkers for guiding treatment selection in advanced HCC remain largely unavailable.
  • The REACH-2 trial highlighted ramucirumab's efficacy in a specific HCC patient subgroup.

Purpose of the Study:

  • To review current knowledge on HCC carcinogenesis and the VEGF/VEGFR-2 pathway.
  • To discuss the clinical development of ramucirumab in advanced HCC.
  • To critically assess previous trial gaps and propose modernizations for clinical trials and personalized HCC therapy.

Main Methods:

  • Review of existing literature on HCC, VEGF/VEGFR-2 pathways, and ramucirumab clinical trials.
  • Analysis of data from the REACH-2 trial regarding ramucirumab efficacy.
  • Critical evaluation of a previous negative phase III trial in advanced HCC.

Main Results:

  • Ramucirumab, a VEGFR-2 inhibitor, demonstrated overall survival superiority against placebo in the REACH-2 trial for second-line HCC treatment.
  • This benefit was observed in patients with alpha-fetoprotein (AFP) levels greater than 400 ng/ml.
  • The study identifies a need for predictive biomarkers to personalize advanced HCC treatment.

Conclusions:

  • Ramucirumab represents a significant advancement in second-line treatment for a specific population of advanced HCC patients.
  • Understanding HCC angiogenesis and VEGF/VEGFR-2 pathways is crucial for developing targeted therapies.
  • Modernizing clinical trial designs and incorporating biomarker strategies are essential for advancing personalized medicine in advanced HCC.
Keywords:
AlphafetoproteinHCCRamucirumab

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