In patients with advanced hepatocellular carcinoma who fail to respond completely to sorafenib, the immune checkpoint inhibitor nivolumab (Opdivo, Bristol Myers Squibb/Ono Pharmaceuticals) provides a durable response, according to interim results from the phase 1/2 CheckMate 040 study (NCT01658878).
Currently, the multikinase inhibitor sorafenib (Nexavar, Bayer) is the only approved treatment for patients with advanced disease, said investigator Jörg Trojan, MD, from Klinikum der Johann Wolfgang Goethe-Universität in Frankfurt, Germany. It is indicated for people with advanced liver cancer for whom surgery is not an option.
"Most patients progress or have some intolerability to sorafenib, and we have no other approved treatment options available," he explained.
This is a concern because hepatocellular carcinoma is among leading causes of cancer-related deaths in the world, and about 850,000 new cases are diagnosed each year.
CheckMate 040, which began in 2015, is ongoing. Dr Trojan presented data on a subgroup of patients followed until November 2016 here at the International Liver Congress 2017, but for results published online to coincide with the presentation, the cutoff was August 2016.
All 214 patients in the dose-expansion phase of the study had advanced hepatocellular carcinoma and were treated with nivolumab 3 mg/kg. That dose was chosen after a dose-escalation phase involving 48 patients.
Some of the patients were infected with hepatitis B virus, some with hepatitis C virus, and some had no infection. Some patients been treated previously with sorafenib, and others had not.
"This is the first study in which chronic hepatitis B patients were allowed to enter if they were on concomitant antiviral therapy, as long as the viral load was below 100 units," Dr Trojan pointed out.
Of the 145 treatment-experienced study participants, about 90% had progressed on sorafenib and about 10% had developed intolerance to it.
Looking at individual tumor burden over time, for those who responded, there was tumor shrinking of more than 30%.
In this group, the overall objective response rate with nivolumab was 14.5%. It is important to note that "another 40% achieved disease stability, so there was a disease control rate of nearly 55%," he reported.
In November 2016, at a median follow-up of 12.9 months, 27% of hepatitis C patients and 18% of uninfected patients were still receiving nivolumab. "If response is occurring, it's lasting, and the median duration of initial response was not reached yet in those patients," he explained.
Median time to response — the primary end point — was 2.8 months, regardless of whether or not patients were infected with hepatitis.
"Looking at individual tumor burden over time, for those who responded, there was tumor shrinking of more than 30%," Dr Trojan said.
Responses were independent of tumor cell programmed death-ligand 1 (PD-L1) expression. "In other studies, PD-L1 has some predictive values," he explained, "but not in hepatocellular carcinoma, at least not in our study."
The adverse-effect profile of nivolumab was consistent with other tumor studies, and so far no new safety signals have emerged. "In general, it was well tolerated," Dr Trojan said.
"Nivolumab is a drug that acts by modulating the immune system, and immunotherapy is one of the most attractive approaches for fighting cancer," said Alejandro Forner, MD, PhD, from the Hospital Clinic Barcelona in Spain, who is a member of the scientific committee for the European Association for the Study of the Liver.
In this study, "nivolumab was demonstrated to be safe and it showed a promising overall survival, justifying the further evaluation of this drug in larger studies," he told Medscape Medical News.
"In sorafenib-experienced patients with or without chronic viral hepatitis, nivolumab has demonstrated durable objective responses, regardless of the underlying liver disease," Dr Trojan said.
The phase 3 CheckMate 459 study (NCT02576509) is currently comparing nivolumab with sorafenib as a first-line treatment for patients with advanced hepatocellular carcinoma, he added.
Bristol-Myers Squibb and Ono Pharmaceuticals sponsored this study. Dr Trojan reports receiving consulting and/or lecture fees from Bristol-Myers Squibb and Bayer Healthcare. Dr Forner has disclosed no relevant financial relationships.