Immunotherapy plus arterial infusion chemotherapy shows promise for advanced liver cancer

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.

This 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 studies.

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.

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 extrahepatic metastasis.

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 were reassessed.

Thirteen patients experienced partial tumour shrinkage, for an overall response rate of 44.8%. Another 11 had stable disease, yielding a disease control rate of 82.7%.

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 remission.

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 activity.

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 liver cancer.

"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."