New Therapy Improves Survival in Hepatoma With Portal-Vein Invasion

By Will Boggs MD

May 29, 2019

NEW YORK (Reuters Health) - In patients with hepatocellular carcinoma (HCC) and portal-vein invasion, sorafenib combined with hepatic arterial infusion chemotherapy (HAIC) improves overall survival compared with sorafenib alone, researchers from China report.

"Sorafenib has been a standard treatment of advanced hepatocellular carcinoma for the past 10 years. Multiple randomized clinical trials on novel drugs have been conducted to challenge the role of sorafenib, but so far there have been no agents which clearly beat sorafenib. The study not only demonstrates a survival benefit, but the magnitude of >6-month improvement with hazard ratio of 0.3+ is very impressive," said Dr. Steven L. Chan from The Chinese University of Hong Kong, who who recently reviewed the management of HCC with portal-vein tumor thrombosis but was not involved in the new study.

Dr. Ming Shi from the Collaborative Innovation Center for Cancer Medicine in Guangzhou, senior author on the new study, told Reuters Health by email that clinical guidelines from the Japan Society of Hepatology "recommend HAIC as one of the standard treatment options for patients with HCC and portal-vein tumor thrombus. But so far, some physicians still have doubts about the efficacy of HAIC."

Dr. Shi and colleagues compared sorafenib plus HAIC with oxaliplatin, fluorouracil, and leucovorin (FOLFOX) versus sorafenib monotherapy in their randomized, open-label phase 3 trial involving 247 patients (90% male) with HCC and portal-vein invasion.

Median overall survival was 13.37 months in the sorafenib plus HAIC group and 7.13 months in the sorafenib monotherapy group (hazard ratio, 0.35; P<0.001), the team reports in JAMA Oncology, online May 9.

Overall survival rates with sorafenib plus HAIC were 96% at three months, 82.4% at six months, and 65.6% at 9 months versus 87.7%, 59.0%, and 24.6%, respectively, with sorafenib monotherapy.

Median overall survival was significantly longer with sorafenib plus HAIC than with sorafenib monotherapy in patients stratified by the grade of portal-vein invasion.

Patients in the sorafenib plus HAIC group also had significantly longer median progression-free survival (7.03 months vs. 2.6 months) and median intrahepatic progression-free survival (8.07 months vs. 3.1 months, respectively), and higher overall response rates (40.8% vs. 2.46%, respectively).

Among the 35 patients in the sorafenib monotherapy group who crossed over to the sorafenib plus HAIC group, the median overall survival was longer (9.47 months) than that in patients who did not cross over (5.53 months).

The overall incidence of treatment-related adverse events was similar in the sorafenib plus HAIC and sorafenib monotherapy groups.

"I hope that our research will help physicians reevaluate the benefits that HAIC may bring to patients with advanced hepatocellular carcinoma," Dr. Shi said.

"I think that medical oncologists and radiologists should strengthen their communication and cooperation to further optimize the systemic and local treatment combinations of hepatocellular carcinoma," he said. "Future studies are warranted to evaluate HAIC in combination with other drugs, such as lenvatinib, programmed cell death protein-1 antibody. Also needed is study comparing HAIC with transarterial chemoembolization (TACE, the current standard of care) for intermediate-stage hepatocellular carcinoma."

"With positive results from the current phase 3 trial, sorafenib plus HAIC may become another treatment option for patients in China with newly diagnosed advanced HCC with portal vein thrombosis," write Dr. Andrew X. Zhu and colleagues from Massachusetts General Hospital Cancer Center and Harvard Medical School, in Boston, in a linked editorial. They also note that the results may not be applicable to patients with non-hepatitis B virus-related HCC, Western and other Asian populations, and women.

And Dr. Chan pointed out in his email, "The systemic treatment option for HCC is evolving rapidly, with emerging data on the area of immunotherapy and novel targeted agents (apart from sorafenib). It is expected that HCC patients will undergo multiple lines of sequential immunotherapy and targeted agents. The role of HAIC + sorafenib regimen is unclear in the context of these 'modern' treatments/sequences."

SOURCE: https://bit.ly/2VXi8jS and https://bit.ly/2M0TwSG

JAMA Oncol 2019.

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