CHICAGO — Nivolumab appeared safe and effective for the treatment of patients with advanced hepatocellular carcinoma, according to interim study results presented at the ASCO Annual Meeting.
The responses observed with nivolumab (Opdivo, Bristol-Myers Squibb) — a programmed cell death-1 (PD-1) antibody — also appeared durable, results showed.
“This is a worldwide problem, with 780,000 people diagnosed with liver cancer annually,” Anthony B. El-Khoueiry, MD, associate professor of clinical medicine and phase 1 program director at the University of South California Norris Comprehensive Cancer Center, said during a press conference. “For patients with advanced disease, who are the majority of patients we see, sorafenib (Nexavar; Bayer, Onyx) is the only FDA-approved systemic treatment, with an average survival of less than 11 months. After failure of sorafenib, there is no current standard of care.”
El-Khoueiry and colleagues evaluated data from 47 patients with advanced hepatocellular carcinoma who had a Child-Pugh score of 5 or 6 and an ECOG performance status of 0 or 1. Seventy-five percent of patients had undergone prior systemic therapy, and 68% had received sorafenib.
Researchers divided patients into three cohorts. One included patients with hepatitis C (n = 12), a second included patients with hepatitis B (n = 11), and a third consisted of uninfected patients (n = 24).
“The reason patients were treated in separate cohorts was to ensure that nivolumab was safe in all these groups of patients,” El-Khoueiry said. “The dose was escalated separately in each group.”
Patients received 0.1 mg/kg to 10 mg/kg IV nivolumab in parallel dose-escalation cohorts for up to 2 years.
Safety served as the study’s primary endpoint. Antitumor activity — assessed using modified RECIST criteria — served as the secondary endpoint.
Nivolumab appeared well tolerated in patients with ongoing hepatitis B and C infections, and researchers observed no safety concerns related to flares of hepatitis B infection or worsening viral infection.
Most adverse events were mild, El-Khoueiry said. Sixty-eight percent of patients experienced a drug-related adverse event, and 19% experienced grade 3 or grade 4 events. The most commonly reported adverse events included aspartate aminotransferase increase (19%); rash (17%); elevation of alanine aminotransferase (15%), lipase (17%) and amylase (15%); and pruritus (13%).
The most common grade 3 or grade 4 adverse events included aspartate aminotransferase increase (11%), alanine aminotransferase increase (9%) and lipase increase (9%).
One patient who received the 10-mg/kg dose experienced a dose-limiting toxicity; however, researchers did not define the maximum tolerated dose in any cohort.
Of 42 patients evaluable for response, 21 were uninfected and 21 were viral infected. Eight patients achieved objective tumor shrinkage beyond 30%, which equated to an objective response rate of 19%.
“To put this into context, the response rate with the standard of care currently, sorafenib, is 2% to 3%,” El-Khoueiry said.
Two patients — both uninfected — achieved a complete response, with responses ongoing past 12 months. Six patients, five of whom were viral infected, achieved a partial response.
Of the eight total responders, six had an ongoing response at the time of the analysis, and 50% of responses lasted longer than 12 months.
Forty-eight percent of patients experienced stalled tumor growth, and the longest duration of tumor stabilization has extended beyond 17 months.
Sixty-two percent of patients achieved 12-month OS. The 1-year OS rate among patients who have already received sorafenib typically is only 30%, El-Khoueiry said.
“We are encouraged to see that nivolumab was safe overall, and the response rate as well as preliminary survival data look quite promising,” El-Khoueiry said in a press release. “While we have to verify this early signal in larger studies, this is one of the first signs that immunotherapy with immune checkpoint inhibitors will have a role in the treatment of liver cancer.”
An expansion part of the study is ongoing to confirm these findings, El-Khoueiry said. – by Alexandra Todak
El-Khoueiry AB, et al. Abstract LBA101. Presented at: ASCO Annual Meeting. May 29-June 2, 2015; Chicago.