Molecular heterogeneity in hepatocellular carcinoma.

Abstract

Recent successful clinical trials have led to or likely lead to the regulatory approval of several molecular targeted agents for firstand second-line treatment of hepatocellular carcinoma (HCC), including multikinase inhibitors, lenvatinib, regorafenib and cabozantinib, as well as immune checkpoint inhibitors nivolumab and pembrolizumab [1–5]. However, objective response rates to these agents are only 20% at maximum and patient survival benefit is no more than a few months despite the high cost of the drugs. A recent simulation-based analysis has reported that regorafenib treatment for advanced-stage HCC patients is not cost-effective with an incremental cost-effectiveness ratio (ICER) of $224,396 per quality-adjusted life year gained, which far exceeds the widely accepted incremental cost-effectiveness ratio cutoff of $50,000 [6]. Given that only small proportion of the patients respond to each therapy, it is critical to identify potential responders to avoid prescribing the drugs to patients who will not benefit from the treatment and enable cost-effective patient management [7]. However, no biomarker of drug response is available for any of the approved drugs for HCC to date.