Comparable Treatment Outcomes Are Observed for Child-Pugh B in HCC

Pierre Gholam, MD, associate professor of medicine at Case Western Reserve University School of Medicine, and director of the multidisciplinary hepatobiliary tumor team at University Hospitals Seidman Cancer Center in Cleveland, Ohio, examines the limited trial data on treatment for patients with hepatocellular carcinoma (HCC) with worse Child-Pugh scores.

Most major trials in the unresectable setting did not enroll patients with Child-Pugh scores of B or C representing more severe cirrhosis, Gholam says. However, some efforts have been made to evaluate outcomes in terms of tolerability and efficacy based on subgroup and retrospective data.

In subset analysis of the REFLECT trial (NCT01761266) comparing lenvatinib (Lenvima) and sorafenib (Nexavar), patients who initially had Child-Pugh A but developed Child-Pugh B status within 8 weeks of treatment showed a similar rate of benefit with lenvatinib vs sorafenib though their outcomes might be worse overall due to their condition.

Another example was the CELESTIAL trial (NCT01908426) of cabozantinib (Cabometyx) vs placebo in the second line. Those who had Child-Pugh B cirrhosis at 8 weeks were found to have efficacy and tolerability consistent with the overall population. Although this is a difficult population to evaluation prospectively, analyses like these show potential for further efforts to treat these patients.

TRANSCRIPTION:

0:10 | In the unresectable space, there unfortunately have not been a ton of trials looking at patients who have more significant liver dysfunction, such as Child-Pugh B and certainly Child-Pugh C disease. There have been attempts to understand what the potential tolerability and efficacy of various systemic treatments would be in the setting of progressing liver disease.

These have been documented both in first line and in second line and first line subset analysis of the REFLECT trial for example, for lenvatinib suggests that while one understandably would expect a lower survival because the patient has more advanced liver disease, the overall rate of benefit compared to the comparator arm, which in that particular case was sorafenib, as well as the overall burden of adverse events, is not dramatically different in the context of patients who develop Child-Pugh B disease within 8 weeks after initiation of participation in the trial.

1:20 | There are other examples of this, even in second line. One example is…cabozantinib in second line in patients who have unresectable HCC and participated in the CELESTIAL trial. Similar data have been shown in that subset of patients, when compared in this particular case, to the placebo.