The impact of sorafenib in treating patients with advanced hepatocellular cancer may be dependent on their hepatitis status, according to a meta-analysis of patient-level data from three large prospective clinical trials using sorafenib as the control treatment.

The analysis indicated that sorafenib had a favorable effect on overall survival for hepatocellular carcinoma patients who were positive for hepatitis C (HCV), but negative for hepatitis B (HBV) only.

For HCV-positive/HBV-negative patients with advanced unresectable hepatocellular carcinoma (aHCC) who received sorafenib, median unadjusted survival was 12.6 months, compared to 10.2 months for patients who received other treatments, yielding a log hazard ratio of –0.27 (95% confidence interval [CI] –0.46 to –0.06).

Though the study did not shed light on the reasons for this difference in overall survival (OS), the results were seen consistently in data from all trials, and sorafenib did not confer any significant survival benefit for individuals who were not HCV positive and HBV negative. “Irrespective of the mechanism, our data suggest that in future trials in aHCC, particularly where sorafenib is the control arm, there should be stratification according to etiology,” wrote Richard Jackson, MSc, and his coauthors (J Clin Oncol. 2017 Jan 3:JCO2016695197 [Epub ahead of print]).

Mr. Jackson, a medical statistician with the Institute of Translational Medicine at the University of Liverpool, England, and his collaborators examined data from 3,256 patients with aHCC. Of these, 1,643 (50%) received sorafenib. The remainder was aggregated into an “other treatment” group, pooling data from patients who received brivanib, sunitinib, and linifanib.

All patients were also divided into four etiologic subgroups: HBV-negative/HCV-negative; HBV-negative/HCV-positive; HBV-positive/HCV-negative; and HBV-positive/HCV-positive. Mr. Jackson and his colleagues then examined the pooled data to see what effect treatment type (sorafenib versus pooled comparator treatments) had on overall survival for each etiologic subgroup. They found no statistically significant survival benefit for sorafenib in the three etiologic subgroups that were not HCV positive/HBV negative, though the data showed a statistically insignificant trend favoring sorafenib. Race, when examined as a potential confounding factor, was not associated with a difference in OS benefit for sorafenib.

The sponsors of three large clinical trials of treatments for aHCC that used sorafenib as the control arm provided deidentified patient-level data to the study’s authors, who then undertook an individual patient data (IPD) meta-analysis. “IPD meta-analyses have a major advantage over aggregate meta-analyses in that they ensure consistent analytic techniques and allow for detailed inspection of interaction of subgroup effects that are not available in published evidence,” wrote Mr. Jackson and his coauthors.

In discussing their findings, the researchers called for more of the data-sharing that allowed their IPD meta-analysis, citing a proposal on the topic from the International Committee of Medical Journal Editors. “[O]ur study showed how the benefits of access to completed trial data are not necessarily confined to reanalysis of the original hypothesis tested by the trial. Here, by a meta-analysis, we arrive at an answer to a question that was not considered when the trials were conceived and could not have been answered by any of the trials individually,” they wrote.

The study data were provided by Bristol-Myers Squibb, Pfizer, and AbbVie from studies they sponsored. Mr. Jackson reported no conflicts of interest.

On Twitter @karioakes


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