Abstract
Background Second line of treatment of hepatocellular carcinoma (HCC) has notably changed in recent years as three novel drugs with a different mechanism of action have demonstrated to improve survival compared to placebo; thus, there is a need to better define the profile of optimal candidates to second-line treatment with these drugs in order to maximize clinical benefit. Materials and Methods We performed a pooled analysis from the subgroup analysis of all published phase III trials for approved targeted therapy in the second line of treatment for HCC, with the aim to discover possible clinical-pathological predictive factors. Results Four studies were included in the analysis for a total of 2137 cases whose results supported the use of these novel agents in male patients with ECOG: 0, extrahepatic metastases, and HBV infection. Conclusions Future studies are awaited to define best candidates for novel agents approved in the second line of treatment for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer worldwide and one of the main causes of cancer-related deaths worldwide [1]
All these drugs have enlarged the spectrum of available options for the management of the second line of treatment of advanced hepatocellular carcinoma (HCC), there is still the need to better define the profile of optimal candidates to these drugs in order to maximize clinical benefit. erefore, we performed a pooled analysis from the subgroup analysis of all published phase III trials that reported positive results of novel drugs in the Journal of Oncology
In the REACH trial, the anti-VEGFR2 monoclonal antibody ramucirumab has shown a survival benefit in the prespecified subpopulation of patients with elevated baseline α-fetoprotein concentrations of 400 ng/mL or greater [10]. is was subsequently confirmed in the confirmatory REACH-2 trial that enrolled only patients with baseline α-fetoprotein concentration of 400 ng/mL or greater [13]. Both regorafenib, a VEGFRs, PDGFRs, KIT, and Tie2 inhibitor, and cabozantinib, a VEGFRs, MET, and AXL inhibitor, have shown to increase survival compared to placebo in the RESOURCE and CELESTIAL trials, respectively [11, 12]
Summary
Second line of treatment of hepatocellular carcinoma (HCC) has notably changed in recent years as three novel drugs with a different mechanism of action have demonstrated to improve survival compared to placebo; there is a need to better define the profile of optimal candidates to second-line treatment with these drugs in order to maximize clinical benefit. We performed a pooled analysis from the subgroup analysis of all published phase III trials for approved targeted therapy in the second line of treatment for HCC, with the aim to discover possible clinical-pathological predictive factors. Four studies were included in the analysis for a total of 2137 cases whose results supported the use of these novel agents in male patients with ECOG: 0, extrahepatic metastases, and HBV infection.
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