Thyroid immune-related adverse events correlated with favorable clinical outcome in patients with advanced hepatocellular carcinoma treated with atezolizumab and bevacizumab

Lead Investigator: Hong Jae Chon, CHA Bundang Medical Center
Title of Proposal Research: Thyroid immune-related adverse events correlated with favorable clinical outcome in patients with advanced hepatocellular carcinoma treated with atezolizumab and bevacizumab
Vivli Data Request: 8347
Funding Source: None.
Potential Conflicts of Interest: None.

Summary of the Proposed Research:

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.

Statistical Analysis Plan:

A cohort of IMbrave150 patients will be used to obtain prospective survival data for patients with thyroid irAE after Ate/Bev treatment.

OS was defined as the time from the initiation of treatment until death from any cause. Progression-free survival (PFS) was defined as the time between the initiation of treatment and the progression of the disease or death from any cause. Survival outcomes were analyzed using the Kaplan–Meier method, and the subgroups were compared using the log-rank test. Univariate and multivariate analyses of OS and PFS were performed using the Cox proportional hazards model. Statistical significance was defined as two-sided P < 0.05. Missing data be either excluded.

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

Public Disclosures:

  1. Song, Y.S., Yang, H., Kang, B., Cheon, J., Kim, I., Kim, H., Lee, W.S., Sang, Y.B., Jung, S., Lim, H.Y. and Gaillard, V.E., 2023. Thyroid Dysfunction After Atezolizumab and Bevacizumab is Associated with Favorable Outcomes in Hepatocellular Carcinoma. Doi: 10.1159/000531182
  2. Song, Y.S., Yang, H., Kang, B., Cheon, J., Kim, I., Kim, H., Lee, W.S., Sang, Y.B., Jung, S., Lim, H.Y. and Gaillard, V.E., 2023. 993P – Thyroid Dysfunction After Atezolizumab and Bevacizumab is Associated with Favorable Outcomes in Hepatocellular Carcinoma. Annals of Oncology (2023) 34 (suppl_2): S594-S618. doi: 10.1016/annonc/annonc1327