Regorafenib the drug of choice second-line HCC treatment

Regorafenib may be used as the agent of choice in the second-line treatment of hepatocellular carcinoma (HCC) in sorafenib-intolerant patients, with cabozantinib as a possible alternative, according to a network meta-analysis.

Researchers performed a systematic review of randomized controlled trials evaluating different drugs for the second-line treatment of advanced HCC. Overall survival (OS) was the primary study endpoint, with everolimus selected as the common comparator for efficacy analyses and placebo for safety analyses.

Subgroup analyses estimated OS according to Asian ethnicity, presence of hepatitis B or hepatitis C infection, macrovascular invasion, and extrahepatic metastases. Other outcome variables included progression-free survival (PFS), rates of grade 3–5 adverse events and treatment discontinuation due to adverse events.

The meta-analysis included 13 RCTs, yielding a total of 5,076 patients and evaluating 11 drugs. Pooled data revealed that OS was significantly longer with regorafenib (hazard ratio [HR], 0.60; 95 percent CI, 0.44–0.81) and with cabozantinib (HR, 0.72; 0.55–0.95) than with everolimus. The positive effect of regorafenib on OS tended to persist across patient subgroups.

Regorafenib also significantly prolonged PFS (HR, 0.46; 0.35–0.62) but substantially increased the rates of grade 3–5 adverse events (odds ratio [OR], 3.18; 2.22–4.54) and treatment discontinuation due to adverse events (odds ratio, 2.67; 1.21–5.87).

Advanced HCC accounts for the second leading cause of cancer-related deaths, with either sorafenib or lenvatinib used in the first-line setting, researchers noted. The findings suggest that regorafenib may be better than cabozantinib in the second-line treatment of HCC in patients who cannot tolerate their previous medication.