Study introduces new strategy to treat advanced liver cancer

Advanced liver cancer, or hepatocellular carcinoma (HCC), currently has limited treatment options and poor prognosis • A recent study introduces a new approach to treat advanced HCC by combining systemic immunotherapy with internal radiation therapy

• Advanced liver cancer, or hepatocellular carcinoma (HCC), currently has limited treatment options and poor prognosis
• A recent study introduces a new approach to treat advanced HCC by combining systemic immunotherapy with internal radiation therapy
• Findings indicate this approach can be further explored to treat the disease

Singapore, 27 October 2021 – A Singapore clinical trial has introduced a new way to treat advanced hepatocellular carcinoma (HCC), the most common type of primary liver cancer, by safely combining nivolumab, an immunotherapy drug, and yttrium-90 resin microspheres radioembolisation (Y90-RE), a form of internal radiation therapy. Led by a research team from the National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH), the study presents a novel, potential treatment strategy for intermediate and advanced HCC. Study findings were published in The Lancet Gastroenterology and Hepatology on 22 October 2021.¹

In Singapore, HCC is the third and fourth most common cause of cancer deaths amongst males and females, respectively.² A large proportion of patients are diagnosed at a stage when their cancer can no longer be removed by surgery, and treatment options are limited. This highlights an urgent need to find new ways to improve survival for patients with advanced HCC.

HCC that cannot be surgically removed can be treated with Y90-RE, a minimally invasive treatment that delivers high doses of radiation via the bloodstream directly to the tumour in the liver. Immunotherapy drug, nivolumab, on the other hand, enhances the body’s immune response against cancer cells. It has shown promising results in studies to treat advanced HCC and to enhance the effects of radiation therapy in various cancers. Combination treatment using radiotherapy and immunotherapy to treat HCC is backed by strong scientific data and pre-clinical studies.

This prompted the team to initiate a phase II trial to evaluate the safety and efficacy of combining Y90-RE with nivolumab in 40 patients with advanced, inoperable HCC in 2017. Their ages ranged from 23 to 79 years, and most of them were male (78%). Patients were given nivolumab through an intravenous (IV) infusion 21 days after Y90-RE was administered, and every two weeks thereafter until progression or development of severe toxicities.

Results were measured based on the proportion of patients who had partial or complete response to the therapy. Results showed that these patients had an overall response rate (ORR) of 30.6%, which rose to 43.5% for those with cancer limited only to liver. Most importantly, the team found the combination of Y90-RE followed by nivolumab to be safe and tolerable.

“We are encouraged that this trial has shown that combining Y90-RE and nivolumab is safe and has promising overall response rates in treating advanced primary liver cancer,” said Clinical Assistant Professor David Tai, Senior Consultant, Division of Medical Oncology, NCCS and Principal Investigator of this study. “Our next step is to validate these findings in a larger cohort of patients with advanced liver cancer with no distant spread.”

“The findings of this study augurs well for advanced liver cancer patients who are faced with limited treatment options. If this new combination treatment’s efficacy is further shown in studies from other countries, it would benefit not only those in Singapore, but the region as well, given that liver cancer is a huge problem in this part of the world,” said Clinical Associate Professor David Ng, Head and Senior Consultant, Department of Nuclear Medicine and Molecular Imaging, SGH.

“Our department has many years of experience delivering very safe and highly targeted powerful anti-cancer radiotherapy directly to cancer cells in the liver while sparing the healthy parts of the organ. Patients experience minimal downtime from this almost painless procedure and can often go home on the same or next day. We sincerely hope that the therapeutic synergy provided by combining these two proven treatments will greatly benefit our patients,” said Clinical Assistant Professor Apoorva Gogna, Senior Consultant, Department of Vascular and Interventional Radiology, SGH.

This trial is supported by the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Individual Research Grant (NMRCCIRG/1454/2016), Bristol-Myers Squibb and Sirtex Medical. Nivolumab is manufactured by Bristol-Myers Squibb and yttrium-90 resin microspheres radioembolisation is developed by Sirtex Medical.