Abstract 721P
Background
While the treatment of advanced hepatocellular carcinoma (HCC) has undergone significant changes with the use of immunotherapy, predicting which patients will respond to these regimens remains a challenge. Prior studies have established molecular classifications of HCC based on specific genomic disturbances, suggesting that different subclasses can vary in expected prognoses. However, further investigation is required to clarify the association between molecular alterations and immunotherapy responses.
Methods
We conducted a retrospective study to determine the association between specific mutations in HCC and responses to immunotherapy. All patients underwent genomic profiling on tumor samples or peripheral blood using next-generation sequencing (NGS) assays. Immunotherapy was administered alone or in combination with other systemic treatment.
Results
There was a total of 76 patients included in this study. The most frequently identified mutations were in the TERT promoter (52.6%), TP53 (52.6%), CTNNB1 (34.2%), and ARID1A (28.9%). There were 62 patients who experienced disease control (complete response, partial response, or stable disease) compared to 14 patients with disease progression from immunotherapy. TERT promoter mutations were found in 78.6% of patients who experienced disease progression compared to 46.8% of patients with disease control (p = 0.04). In addition, TP53 mutations were found in a significantly greater proportion of patients who achieved partial or complete responses compared to those who did not (70% vs 41.3%, p = 0.02). See the table for further details. Table: 721P
Molecular alterations and immunotherapy responses
| Disease Progression (n = 14) | Stable Disease (n = 32) | Partial Response (n = 27) | Complete Response (n = 3) | |
| TERT | 11 (78.6%) | 15 (46.9%) | 14 (51.9%) | 0 |
| TP53 | 6 (42.9%) | 13 (40.6%) | 20 (74.1%) | 1 (33.3%) |
| CTNNB1 | 5 (35.7%) | 9 (28.1%) | 11 (40.7%) | 1 (33.3%) |
| ARID1A | 2 (14.3%) | 8 (25%) | 12 (44.4%) | 0 |
Conclusions
In this study, TERT and TP53 mutations in HCC patients were found to have significant correlations with responses from immunotherapy. As the use of immunotherapy and NGS in this population continues to expand, additional prospective studies are needed to clarify the impact of specific mutations on patient outcomes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.