Improvement in median OS in patients with advanced HCC and strict eligibility criteria receiving Sorafenib

Introduction:

Llovet et al. demonstrated within the SHARP-trial that the median overall survival was nearly 3 months prolonged for patients with advanced hepatocellular carcinoma (HCC) and treatment with sorafenib compared to placebo. It is unclear whether patients with modified eligibility criteria (MEC) benefit as well as patients with strict eligibility criteria (SEC) according to the SHARP-criteria.

Methods and Patients:

Within this retrospective single center analysis we initially reviewed electronic records of 987 patient diagnosed with HCC, who were treated between January 2008 and October 2017. Finally, 293 patients received sorafenib and were eligible for final analysis. Data of risk-factors, liver function, BCLC stage, ECOG, laboratory values, radiological findings, treatment modalities, and follow-up were recorded until 31.12.2017. Primary outcomes were median overall survival (OS) of patients with MEC and SEC according to the SHARP-criteria, as well as the safety-profile during treatment. Furthermore, a secondary endpoint was median OS depending on risk-factors.

Results:

The median OS was prolonged with 12.0 months in patients with SEC compared to 10.7 months in the SHARP-trial itself. Even patients with MEC, representing real-life practice, reached a median OS of 10.0 months without disadvantages concerning the safety of the drug. The incidence of drug-related adverse events (mainly grade 1 or 2) was 80.2% in patients with MEC and only 70.0% in patients with SEC compared to 80.0% in the SHARP-trial. Major adverse events included fatigue (36%), diarrhea (35%), and hand-foot skin syndrome (31%). A trend to prolonged median OS was demonstrated in patients with chronic hepatitis C (15.0 months in the MEC-cohort and 25.0 months in the SEC-cohort) compared to alcohol- or hepatitis b (9.0 months and 10.0 months)-related underlying liver disease (p = n.s.).

Conclusion:

Patients with advanced HCC do benefit from systemic treatment with sorafenib under real life conditions reaching a similar outcome. Patients with SEC, according to the SHARP-criteria, displayed an even prolonged median OS, which goes along with previous data from several clinical phase III trials, in which patients receiving sorafenib in a control arm, also demonstrated prolonged OS compared to the SHARP-trial.