WASHINGTON (FRONTLINE MEDICAL NEWS) – A multinational clinical trial has found that the metastatic cancer agent nivolumab can improve long-term survival and durable tumor responses in patients with advanced hepatocellular carcinoma (HCC) whether or not they’ve had previous treatment with a chemotherapy agent already approved for advanced primary liver cancer, a principal investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

“Nivolumab has demonstrated clinically meaningful efficacy across etiologies in sorafenib-naive and -experienced patients with extended follow-up,” Bruno Sangro, MD, of the University of Navarra in Pamplona, Spain, said in reporting results of the CheckMate-040 trial. “The median overall survival is 15 and 15.6 months in patients who were sorafenib-experienced in both the dose-escalation and expansion cohorts.”

The dose-escalation cohort received 0.1 to 10 mg/kg of nivolumab (Opdivo) while the dose-expansion group received a steady dose of 3 mg/kg. In all, 262 patients participated in the trial, 80 of whom had never been on sorafenib (Nexavar) therapy. The survival outcome in these subgroups, Dr. Sangro said, “really speaks for the consistency and the robustness of the results.”

Trial participants had inoperable, usually metastatic HCC, with Child-Pugh scores up to and including 7 in the escalation group or up to and including 6 in the expansion group. Most of them were progressing to treatment with one or more prior systemic therapies, including sorafenib. Their aspartate aminotransferase and alanine aminotransferase scores were in the upper limits of normal, and bilirubin was less than or equal to 3 mg/dL. If they had hepatitis B (HBV), their viral load had to be less than 100 IU/mL and they had to be on effective antiviral therapy. Any history of hepatic encephalopathy or clinically significant ascites and an active HBV and hepatitis C (HCV) coinfection were grounds for exclusion.

“Most patients had to discontinue nivolumab because of disease progression,” Dr. Sangro noted, so that only 36 patients, or 14%, were continuing treatment at the time of this analysis. Thirteen patients in the total population that discontinued nivolumab did so because of toxicity, he said.

“Around 20% of patients achieved an objective remission that included complete responses in all subgroups of patients; 15% of progressors and 23% of sorafenib-intolerant patients had an objective response,” Dr. Sangro said. In terms of overall response, about half of all patients in the sorafenib-experienced subgroups had a complete or partial response or stable disease: 51% in the dose-escalation subgroup and 54% in the dose-expansion subgroup.

Although tumor responses were associated with declines in alpha-fetoprotein levels, “it’s unlikely that these biomarkers will be useful either for monitoring or selecting patients for treatment,” he added. “Indeed, baseline alpha-fetoprotein levels were comparable between responders and nonresponders to nivolumab” Dr. Sangro said.

“We also showed there was some impact on HCV viral kinetics in infected individuals,” Dr. Sangro noted. “The overall safety profile for the HCC population is consistent with other tumor types in which nivolumab is approved; these include patients who are infected with hepatitis B or C viruses.”

The study showed that 36% (19/53) of HCV infected patients had a greater than 1 log decrease in viral load. No signs of additional antiviral activity were detected among HBV-infected patients already on effective antiviral treatment: only 5% (3/59) posted a up to 1 log decrease in HB surface antigen levels, and 11% (7/64) of patients had increases in viral load. “These increases occurred in the setting of low-level viremia.” Dr. Sangro said. “They were asymptomatic and [nivolumab] did not result in changes in hepatic parameters or other serious adverse events.”

With regard to adverse events (AEs), 77% of all patients had some treatment-related AEs, ranging from fatigue to rash to dry mouth to increased lab levels, but only 20% were grade 3 or 4, and 88% of those resolved in an average of 8 weeks, Dr. Sangro said.

More research into nivolumab for HCC is needed, Dr. Sangro said. “Ongoing and future studies in patients with advanced tumors will evaluate nivolumab in the first-line setting or in combination with other agents,” he said.

Dr. Sangro disclosed relationships with Bayer Schering Pharma, Onxeo, Astra Zeneca, and Bristol-Myers Squibb. Bristol-Myers Squibb funded the trial, and Chrysalis Medical Communications assisted in reporting the study results.