Thyroid irAE correlated with favorable clinical outcome in patients with advanced hepatocellular carcinoma treated with atezolizumab and bevacizumab

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is the fourth most common cause of cancer-related deaths worldwide. Many of these cases occur in Asia. Many patients with HCC are diagnosed at an advanced stage, when systemic therapy is the only available treatment option.

Recently, a novel class of immunotherapeutic agents, called immune checkpoint inhibitors (ICIs), was developed for cancer therapy. Among ICIs, antibodies targeting programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T lymphocyte associated protein 4 (CTLA-4) were highlighted for their efficacy and safety in treating patients with various cancer types. Atezolizumab (Ate), an anti-PD-L1 antibody, and bevacizumab (Bev), anti-VEGF antibody, combination therapy has become the standard of care for HCC.

Thyroid immune-related adverse event (irAE) is an adverse event that occurs frequently after treatment with ICIs such as atezolizumab. Patients with thyroid irAE show hypothyroidism or hyperthyroidism, and these patients should be treated. The exact mechanisms of thyroid irAEs have not been fully elucidated yet, but they are assumed to be caused by bystander effects of ICI-induced T-cell activation. It has been reported that approximately 10% of patients treated with Ate/Bev develop thyroid irAE. However, there has been no study that analyzed the relationship between thyroid irAE after Ate/Bev and survival outcomes.

We analyzed 250 patients with advanced HCC who were treated with Ate/Bev at our institute and found that patients with thyroid irAE had significantly better progression free survival (PFS), which is the length of time during and after the treatment of a disease, that a patient lives with the disease but it does not get worse. We will validate these results in a cohort of patients in the IMbrave150 study. We will compare the survival outcomes of patients in the IMbrave150 study with thyroid irAE after Ate/Bev treatment with those without thyroid irAE.