Cara Yap, 7 April 2021
Study start date: Nov 2018
This is a randomised, double-blind, placebo-controlled, global Phase III study to determine the efficacy and safety of transarterial chemoembolization (TACE) treatment in combination with durvalumab monotherapy or TACE given with durvalumab plus bevacizumab therapy compared to TACE therapy alone in patients with locoregional hepatocellular carcinoma not amenable to curative therapy. The study is being conducted in multiple locations, including Asia, the Asia Pacific, north and south Americas and Europe.
Dr Choo Su Pin, BMedSci, BMBS(Nottm), MRCP(UK), FAMS; medical oncologist, Curie Oncology
Dr Choo Su Pin (above) is a medical oncologist who specialises in gastrointestinal cancers including colorectal, upper gastrointestinal, pancreas, hepatobiliary, peritoneal, and anal cancers. She is a key opinion leader in hepatobiliary cancers. Dr Choo was the President of the Singapore Society of Oncology (SSO). She was the Deputy Head of the Division of Medical Oncology prior to private practice and Chief of the Gastrointestinal Cancer Department at National Cancer Centre from 2012 to 2018. She has publications in high impact journals such as Lancet, Nature Genetics, Journal of Clinical Oncology, Annals of Oncology and Cancer Discovery.
*Intended readers: healthcare and industry professionals
For intermediate stage Hepatocellular Carcinoma (HCC), Transarterial Chemoembolization (TACE) therapy has largely been the standard of care. However, we know that while TACE alone may improve disease control in some patients, it is often not curative. The majority of patients experience disease progression while on TACE, or may eventually become ineligible for further TACE therapy. We already know that the combination of immune checkpoint blockers with TACE therapy may have synergistic effects - combining an anti-PD-1 and anti-VEGF drug is now the standard of care in advanced stage HCC - so it makes sense to try to explore a similar effective systemic therapy to treat an earlier stage of the disease. We are looking at whether combining immune checkpoint blockers with TACE in intermediate stage liver cancer will result in better clinical outcomes.
There are similar studies being conducted across different drug companies, with variations in the types of immune checkpoint blockers being used. This trial is unique in using Durvalumab and Bevacizumab with TACE therapy.
TACE therapy can provide control of the cancer but is seldom curative. It is usually just a matter of time before the patient’s disease progresses again. There is a limit to the number of times you can use TACE therapy on individual patients, as there is always concern about the deterioration of liver function with excessive TACE.
Patients who would otherwise be prescribed TACE are eligible. Patients just need to have a confirmed HCC diagnosis and be unsuitable for curative treatment. Only those who have never had TACE therapy are eligible. Participants need to have good liver function, and cannot have disease outside the liver.
Progression free survival is the primary objective, though we will also look at secondary objectives such as overall survival and the time it takes for physical functioning to deteriorate. Patients will be on the trial as long as the treatment is working, and there are no reasons - medical or otherwise - preventing them from remaining on the trial.
This study will explore three arms - patients in one arm will receive standard TACE therapy alone. In a second arm, patients will receive TACE therapy plus the anti-PD-L1 Durvalumab, followed by Durvalumab alone. In the third arm, patients will receive TACE plus Durvalumab and bevacizumab, which is the anti-VEGF drug. We will look at the efficacy of the different treatments in promoting cancer-free survival.
It is good for patients to understand that they will receive standard of care, which is TACE therapy, regardless of which arm of the trial they are in. There is a possibility that they may receive immunotherapy and anti-VEGF therapy on top of TACE, the combination of which has been shown to be effective in treating advanced stage liver cancer. Participating in the trial means that patients are volunteering to be a study subject, so treatment will be covered by the sponsor. Prior to trial enrolment, any potential side effects will be discussed with them.
*The content in this article is purely educational and written for healthcare professionals. It does not contain forward-looking statements, or those specific to commercial enterprise.