Nivolumab Not Superior to Sorafenib in Hepatocellular Cancer

The new standard of care first-line treatment for advanced hepatocellular cancer (HCC) is the combination of atezolizumab and bevacizumab, which replaced first-line sorafenib or lenvatinib. The combination of ipilimumab and nivolumab received regulatory approval for HCC based on phase 2 evaluation.

Investigators now report results of an international, industry-sponsored, open-label phase 3 trial comparing nivolumab to sorafenib in the first-line treatment of advanced HCC. Patients with Child-Pugh class A HCC who had not received prior systemic therapy were randomized to nivolumab 240 mg intravenously every 2 weeks or sorafenib 400 mg orally twice daily. Of 743 patients, median age was 65, most (85%) were men, most (60%) were treated in the U.S. and Europe, 31% were infected with hepatitis B and 23% with hepatitis C, and 58% had extrahepatic disease. PDL-1 score in tumor cells (TPS) was <1% in 82% of patients.

At a minimum follow up of 22.8 months, median overall survival did not differ significantly in the nivolumab and sorafenib arms (16.4 and 14.7 months; hazard ratio, 0.85; P=0.075). There was also no difference in median time to progression (3.8 and 3.9 months). The response rate was numerically but not significantly higher for nivolumab compared with sorafenib (16% and 7%); disease control rates were similar (55% and 58%). Outcomes trended better in the minority of patients who were TPS positive. No new safety signals were observed.