Treatment Efficacy Differences of Sorafenib for Advanced Hepatocellular Carcinoma: A Meta-Analysis of Randomized Clinical Trials

Abstract

Objectives: Hepatocellular carcinoma (HCC) is a heterogeneous disease. We explored whether any specific subgroups of patients may gain more survival benefits from sorafenib as the first-line therapy for advanced HCC. Methods: PubMed and the Cochrane library were searched for phase III clinical trials that compared sorafenib with other treatments as first-line therapy for advanced HCC. We retrieved data from the published articles and then calculated synthesized hazard ratios (HRs) of overall mortality for patients of different subgroups, using patients who received other treatments as the reference. Results: Four phase III clinical trials comparing sorafenib with other treatments were included in this study. The HRs were not significantly different between patients from various geographic regions (p = 0.183), patients with different Eastern Cooperative Oncology Group performance statuses (p = 0.699), or patients with different tumor involvement (p = 0.221). By contrast, the synthesized HR for hepatitis C virus (HCV)+ patients was 0.65 [95% confidence interval (CI) 0.53-0.80], which was significantly lower than that for HCV- patients (0.87, 95% CI 0.79-0.96, p = 0.013). Conclusions: As the first-line therapy for advanced HCC, sorafenib might provide more survival benefits to HCV+ patients than to HCV- patients.

Alternative treatment strategies to sorafenib in patients with advanced hepatocellular carcinoma: a meta-analysis of randomized Phase III trials

“…However, there was a trend of patients treated with sorafenib who were HCV-infected having increased hazard than those treated with other TKIs, although this showed no statistically significant evidence. Consistently, Shao et al and Jackson et al reported improved OS for patients positive for HCV when treated with sorafenib, but no evidence of any improvement in OS attributable to sorafenib for patients positive for HBV and negative for HCV 18,20. Meanwhile, a retrospective study of patients who received sorafenib for advanced HCC found that HCV infection but not ethnicity was associated with OS 24.…”

“…Our meta-analysis included more data than previous meta-analyses, in which recent published clinical trials have not been updated 12,15,16,18–20. In addition, our meta-analysis included randomized Phase III trials only.…”

Complete Response to Full-Dose Sorafenib Treatment in an Elderly HCC Patient: a Case Report

“…Our patient presented an infection by HCV: a number of studies have shown that the efficacy of sorafenib is increased in patients who are infected by this virus [10][11][12], partly due to the potential inhibition exerted by sorafenib on HCV replication [13]. The identification of biomarkers and predictors of survival, such as alpha-fetoprotein, currently represents a major line of research [14,15].…”

Hepatocellular Carcinoma: A Global Disease in Need of Individualized Treatment Strategies

“…Evidence suggests that, similar to other oncology fields, a one-size-fits-all approach is not appropriate in HCC. Many data gained on clinical grounds hint at optimizing sorafenib therapy (or subsequent therapies), for instance, according to HCV status, 8 a-fetoprotein response 9 and a-fetoprotein levels, patterns of disease progression, 10 or reasons for sorafenib discontinuation. 10 As a matter of fact, because nearly 30% of patients eligible for second-line treatments permanently discontinue sorafenib as a result of an adverse event, a sound inclusion criterion of the Regorafenib After Sorafenib in Patients with Hepatocellular Carcinoma (RESORCE) study of regorafenib versus placebo was to limit the enrollment only to those patients who could tolerate sorafenib.…”