Trajectories of alpha-fetoprotein and liver cancer outcomes after atezolizumab treatment

Lead Investigator: Linbin Lu, the 900th Hospital of PLA
Title of Proposal Research: Trajectories of alpha-fetoprotein and liver cancer outcomes after atezolizumab treatment
Vivli Data Request: 7822
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

The project background:
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, ranks the third leading cause of cancer-related death worldwide, with chronic hepatitis B virus (HBV) infection for key determinants in China. The level of α-fetoprotein (AFP) in the blood is most commonly used for detecting and clinical follow-up of patients with HCC. To further explore the new utility of this old marker, the level of AFP in the blood  (over 20% decrease after therapy) is employed to predict treatment response and survival among the HCC patients undergoing chemotherapy and receiving sorafenib, cabozantinib, ramucirumab, which are  all drugs that are approved to treat different types of cancer, and PD-L1 (programmed death ligand-1) inhibitors, which are a group of anticancer drugs that block the activity of Programmed death-1 (PD-1)proteins which are present on the surface of cells and can prevent the body’s immune system from attacking cancer cells.

Necessity of the research:
The role of AFP change, including change over time, is still unclear and poorly defined, with an urgent need to identify the change over time of AFP for HCC. Our previous work found a novel AFP serological response curve for intermediate-stage HCC after transarterial chemoembolization (TACE).TACE is a 2-part treatment for liver cancer where high doses of chemotherapy are given to the tumor to destroy cancer cells, and the blood supply to the tumor is blocked so that it is starved of oxygen and the nutrients it needs to grow.

However, whether AFP serological response curve is an optimal biomarker for advanced HCC treated with PD-1 inhibitors is still unknown.

How the research will add to medical science or patient care:
In our previous study, three distinct trajectories of AFP levels in the blood were identified high-rising, low-stable, and sharp-falling. Of note, we found that about 10- fold difference in death risk existed between AFP high-rising and sharp-falling group. Because there is still no ideal biomarker for HCC treated with PD-1 inhibitors, to validate AFP serological response in advanced HCC is an urgent need.

How the research will be conducted:
In this longitudinal, multicenter, randomized controlled trial, we aim to characterize trajectories of AFP and examine its impact on clinical outcomes for HCC patients treated with PD-1 inhibitors.

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