Lead Investigator: Tim Greten, Center for Cancer Research, National Cancer Institute, NIH
Title of Proposal Research: Locoregional therapy impact on immunotherapy
Vivli Data Request: 9815
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Liver cancer, a disease where abnormal cells grow uncontrollably in the liver, is one of the leading causes of cancer-related death in the world. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Early-stage HCC, without metastasis (spread of the cancer cells) and vascular invasion (when cancer cells infiltrate blood vessels or lymphatic channels) is treated with local therapy, a treatment that targets a specific area of the body affected by cancer. This involves the following:
Surgical resection- a procedure in which a surgeon removes a part or all of a tumor or abnormal tissue from the body, often used in the treatment of cancer.
Ablation therapy (radiofrequency ablation: RFA)- is a minimally invasive procedure that uses heat generated by high-frequency electrical currents to destroy cancerous tissue and catheter therapy
(trans arterial chemoembolization: TACE)- a procedure where chemotherapy drugs are delivered directly into the blood vessels feeding a tumor, followed by the insertion of particles to block the blood supply to the tumor.
HCC typically develops in people with chronic (long-lasting) liver disease caused by hepatitis virus infection or cirrhosis (eg. viral hepatitis, fatty liver), so the recurrence rate of HCC is high and most patients proceed to the advanced stage. In advanced-stage HCC, patients are treated with systematic therapy, treatments delivered throughout the body such as the bloodstream, including immunotherapy, which is a type of cancer treatment that utilizes the body’s natural immune system to recognize and destroy cancer cells.
There is a lot of data supporting the idea that locoregional therapies induce immune responses in HCC. We noticed that the response to immunotherapy tended to be better in the patients who had undergone TACE before enrolling in the clinical trial (pre-TACE patients) in our clinical trial (NCT02821754). Interestingly, blood cytokine and biopsy tissue transcriptome analysis (studying the proteins that signal immune responses in blood and analyzing the activity of genes in tissue samples taken during a biopsy), revealed a more inflamed environment in patients treated with TACE before immunotherapy.
Therefore, we hypothesize that the history of locoregional therapy has an impact on immunotherapy response. This study will add new evidence that will help clinicians to determine the treatment strategy. We will conduct a sub-group analysis using the IMBRAVE150 study and compare the treatment efficacy of pre-TACE patients and others to validate the findings in our trial.
Requested Studies:
A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Data Contributor: Roche
Study ID: NCT03434379
Sponsor ID: YO40245