Results from the phase I/II CheckMate 040 study demonstrated that single-agent nivolumab showed promising clinical activity in patients with Child-Pugh B advanced hepatocellular carcinoma, a population often excluded from advanced HCC trials.
Masatoshi Kudo, MD, PhD
Results from the phase I/II CheckMate 040 study demonstrated that single-agent nivolumab (Opdivo) showed promising clinical activity in patients with Child-Pugh B advanced hepatocellular carcinoma (HCC), a population often excluded from advanced HCC trials.1
Nivolumab is currently approved in the United States for sorafenib-treated patients with Child-Pugh A advanced HCC, based on results from the dose-escalation and dose-expansion phases of CheckMate 040.2
“Many patients with HCC have Child-Pugh B liver function status and have a poorer prognosis compared with Child-Pugh A status,” said Masatoshi Kudo, MD, PhD. “Nivolumab monotherapy demonstrated durable responses in patients with Child-Pugh B advanced HCC.”
Presented at the 2018 Annual Liver Meeting, the data showed that the PD-1 inhibitor was associated with an overall response rate (ORR) of 10.2% using RECIST v1.1 and a disease control rate (DCR) of 55.1% in the study cohort of patients with Child-Pugh status B7 or B8.
Kudo, of the department of gastroenterology and hepatology at Kindai University, delivered the CheckMate 040 findings during the meeting. He added that the safety profile of nivolumab in patients with Child-Pugh B status appears to be comparable to that observed in patients with Child-Pugh A status.
Investigators recruited 49 patients with Child-Pugh B advanced HCC with or without hepatitis C virus or hepatitis B virus. Patients were eligible if they were either naïve to sorafenib, or documented radiographical progression on or intolerance to sorafenib.
Intravenous nivolumab was administered at a flat dose of 240 mg for 30 minutes every 2 weeks. Patients were treated until RECIST v1.1-defined progression or unacceptable toxicity. The primary endpoint was ORR based on investigators assessment, with secondary endpoints including DCR, duration of response, progression-free survival, and overall survival.
The median age of patients was 67 years (range, 40-78) and the majority (75.5%) had a Child-Pugh status B7, compared with 22.4% who had a Child-Pugh status B8.
At the time of data cutoff, the median follow-up period was 11.8 months (range, 6.4-18.0). Forty-one (83.7%) patients discontinued treatment mainly due to disease progression (67.3%), treatment-related adverse events (TRAEs; 4.1%), and death (4.1%). The median duration of treatment was 2.33 months (range, 1.51-4.17).
“Only 2 patients discontinued treatment due to study drug toxicity, [this is] a rate similar to that observed in Child-Pugh A patients,” Kudo added.
The stable disease rate was 44.9%, with 10.2% of patients achieving partial response (PR) and 0% of patients achieving complete response (CR). Comparatively, 40.8% of patients achieved stable disease in Child-Pugh A cohort of the CheckMate 040 study, with 17.2% of patients achieving PR and 3.1% of patients achieving CR.
“Deep responses were observed in some responders, respective of ideology,” he added. “The responders and stable disease patients with Child-Pugh B status show durable response, similar to patients with Child-Pugh A status.”
Two (4.1%) patients had ongoing response at the time of data cutoff. The median DOR was 9.9 months (range, 2.8-9.9) and the median time to response was 2.7 months (range, 1.2-4.2). According to Kudo, 4 of the 5 responders improved from Child-Pugh B7 status to Child-Pugh A5 or A6 status for at least 6 months.
The most common grade 3/4 hepatic TRAEs in the Child-Pugh B cohort were aspartate aminotransferase increase (4.1%), hypertransaminasemia (4.1%), and abnormal hepatic function (2.0%). Kudo added that hepatic TRAEs were seen within the first few months of treatment and the rate of all TRAEs was similar for patients with Child-Pugh B and Child-Pugh A status.
“Nivolumab showed promising efficacy and tolerability in patients with Child-Pugh B status, supporting further investigation in this patient population,” he concluded.