Lead Investigator: Jeroen Dekervel, Universitaire Ziekenhuizen Leuven
Title of Proposal Research: Response Evaluation Criteria in Solid Tumors (RECIST) vs modified RECIST response durability in advanced hepatocellular carcinoma treated with atezolizumab and bevacizumab
Vivli Data Request: 8324
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Every year, more than 900 000 people are diagnosed with liver cancer globally, with the most common form being hepatocellular carcinoma. This cancer type is the third leading cause of cancer deaths worldwide, with a relative 5-year survival rate of approximately 18%.
To evaluate the effect of treatment efficacy in hepatocellular carcinoma, usually, a computerized tomography (CT) or magnetic resonance imaging (MRI) scan is used. Two validated criteria are used to define whether a treatment has an effect on the visualized tumour lesion(s). Historically, the Response Evaluation Criteria in Solid Tumours (RECIST) criteria have been used (as in all other solid tumor types). This system takes into account the change of size of the tumour lesions as a response to the treatment. When shrinkage of tumour lesion(s) is observed beyond a certain cut-off (ie. 30% of initial diameter), this is called a response. Responses can be either partial or complete. When the lesion has increased in size > 20% of the smallest diameter measured, this is progressive disease. All changes between those margins indicate a stable disease.
Specifically for hepatocellular carcinoma, alternative methods to define a treatment effect have been developed; the so-called modified RECIST or mRECIST criteria. These criteria also take into account the intralesional necrosis as response to treatment. Necrosis is the death of body tissue. It occurs when too little blood flows to the tissue. Intralesional necrosis is the death of tissue inside a lesion (a region in an organ or tissue which has suffered damage through injury or disease). The rationale behind these adapted criteria is the fact that certain treatments for HCC (such as treatments with anti-angiogenic properties, e.g. a drug or substance that keeps new blood vessels from forming. In cancer treatment, anti-angiogenesis agents may prevent the growth of new blood vessels that tumors need to grow) induce necrosis of lesions, rather than real tumor shrinkage. Thus, if a tumour lesion does not shrink upon treatment but shows significant intralesional necrosis, this is called an mRECIST response.
We have obtained tissue biopsies prior to treatment with atezolizumab/bevacizumab for molecular analysis and in preliminary findings, we see differences in cancer biology in RECIST vs mRECIST responders. To further explore the differences between the two types of clinical responses, we aim to investigate whether patients that obtain a RECIST response (real tumor shrinkage) have a more durable effect from atezolizumab/bevacizumab compared to patients with an mRECIST response but no RECIST response (pure necrosis without shrinkage).
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