An experimental immune checkpoint inhibitor plus
chemotherapy delivered directly into the hepatic artery in the liver led to
good outcomes in people with locally advanced hepatocellular carcinoma (HCC),
the most common type of liver cancer, according to a report at the 2021 International Liver Congress.
treatment "offers a chance for advanced HCC to be cured," Prof. Li Xu
of Sun Yat-sen University Cancer
Centre in Guangzhou, China, said during a conference press briefing. She added that
outcomes among this group of people with advanced liver cancer were "almost
equal" to outcomes among people with early and middle-stage HCC in other
Chronic hepatitis B or C, heavy alcohol use, fatty
liver disease and other causes of liver injury can lead to the development of
cirrhosis and HCC. Liver cancer is often diagnosed late and is difficult to
treat. It generally responds poorly to traditional chemotherapy, but
immunotherapy has produced favourable outcomes in several studies.
Something that has an
effect outside the liver, for example when viral hepatitis affects the kidneys
or causes depression.
- hepatocellular carcinoma (HCC)
Liver cancer. A long-term complication of chronic inflammation of the liver or cirrhosis.
Partial recovery from an illness, an alternative word for regression.
Xu and her team evaluated the experimental PD-1 checkpoint
inhibitor sintilimab plus hepatic arterial infusion of a
chemotherapy regimen known as FOLFOX in
patients with locally advanced HCC that had invaded the hepatic blood supply
but had not yet spread beyond the liver.
Sintilimab is a monoclonal antibody that helps the immune system
fight cancer. PD-1 is an immune checkpoint protein on T-cells that regulates immune function. Some tumours
can hijack PD-1 to turn off immune responses against them, but PD-1 inhibitors
can restore T-cell activity.
Liver cancer is common in China, most
often due to hepatitis B. China favours a more aggressive approach to liver
cancer treatment, Prof. Xu noted. While surgery is not often used for people
with advanced HCC in western countries, in China surgical resection may be done
in patients with vascular invasion but no
This analysis included 30
patients with locally advanced HCC, most of whom had hepatitis B; one withdrew
from the study. More than 90% were men and the median age was 51 years. Just
over half had a single tumour while 47% had multiple nodules.
The participants received FOLFOX hepatic
arterial infusion chemotherapy (HAIC) plus IV infusions of sintilimab every three weeks. They were assessed after two cycles,
and if their tumours shrank, they were considered for surgery. Those who
underwent surgery continued to received sintilimab every three weeks
until they experienced disease progression or unacceptable toxicity or
completed 16 cycles. Those who were not eligible for surgery received another
two cycles of FOLFOX HAIC plus sintilimab and
Thirteen patients experienced partial tumour shrinkage, for an overall response
rate of 44.8%. Another 11 had stable disease, yielding a disease control rate
Twenty-one of the 29 treated patients (72.4%) became
eligible for surgery, mostly after the first two treatment cycles. Of these, 19
underwent hepatectomy (removal of part of the liver) and two received
radiofrequency ablation (a procedure that uses radio waves to destroy tumours).
Four patients went on to achieve a pathological complete response, or full
Among all treated patients, the median progression-free survival (PFS) time was
15.7 months and the 12-month PFS rate, meaning they were still alive without
disease progression, was 57.9%. The median PFS was just 5.5 months for patients
who did not undergo surgery but was not reached in the surgery group because a
majority were still responding. The 12-month overall survival rate was 82.3%.
Treatment was generally safe but side
effects were common. Although 90% experienced treatment-related adverse events,
these were mostly classified as mild to moderate (grade 1-2). Four people had
severe (grade 3-4) adverse events and one stopped
treatment for this reason. This patient experienced severe immune-related liver
dysfunction, which can result when checkpoint inhibitors restore immune
FOLFOX HAIC plus sintilimab is a "safe and successful conversion
therapy" that provides "outstanding progression-free survival,"
Xu concluded. Although most patients in this study had hepatitis B, she
suggested the same approach might be beneficial for people with other causes of
"We highly recommend that investigators in other
countries do some trials of these new strategies," she said. "Maybe
more and more patients with advanced HCC could be cured."