Clinicogenomic predictors of outcomes in patients with hepatocellular carcinoma treated with immunotherapy Journal Article
| Authors: | Cowzer, D.; Chou, J. F.; Walch, H.; Keane, F.; Khalil, D.; Shia, J.; Do, R. K. G.; Yarmohammadi, H.; Erinjeri, J. P.; El Dika, I.; Yaqubie, A.; Azhari, H.; Gambarin, M.; Hajj, C.; Crane, C.; Wei, A. C.; Jarnagin, W.; Solit, D. B.; Berger, M. F.; O’Reilly, E. M.; Schultz, N.; Chatila, W.; Capanu, M.; Abou-Alfa, G. K.; Harding, J. J. |
| Article Title: | Clinicogenomic predictors of outcomes in patients with hepatocellular carcinoma treated with immunotherapy |
| Abstract: | Introduction: Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes. Methods: The primary objective of this retrospective study was to define the clinical, pathologic, and genomic factors associated with outcomes to ICI therapy in patients with HCC. Patients with histologically confirmed advanced HCC treated with ICI at Memorial Sloan Kettering Cancer Center from 2012 to 2022 were included. Association between clinical, pathological, and genomic characteristics were assessed with univariable and multivariable Cox regression model for progression-free survival (PFS) and OS. Results: Two-hundred and forty-two patients were treated with ICI-based therapy. Patients were predominantly male (82%) with virally mediated HCC (53%) and Child Pugh A score (70%). Median follow-up was 28 months (0.5-78.4). Median PFS for those treated in 1st line, 2nd line and ≥ 3rd line was 4.9 (range: 2.9-6.2), 3.1 (2.3-4.0), and 2.5 (2.1-4.0) months, respectively. Median OS for those treated in 1st line, 2nd line, and ≥ 3rd line was 16 (11-22), 7.5 (6.4-11), and 6.4 (4.6-26) months, respectively. Poor liver function and performance status associated with worse PFS and OS, while viral hepatitis C was associated with favorable outcome. Genetic alterations were not associated with outcomes. Conclusion: Clinicopathologic factors were the major determinates of outcomes for patients with advanced HCC treated with ICI. Molecular profiling did not aid in stratification of ICI outcomes. Future studies should explore alternative biomarkers such as the level of immune activation or the pretreatment composition of the immune tumor microenvironment. © The Author(s) 2024. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; retrospective studies; major clinical study; overall survival; genetics; mortality; chemoembolization; liver cell carcinoma; monotherapy; carcinoma, hepatocellular; liver neoplasms; biomarkers; ipilimumab; ticilimumab; progression free survival; pathology; retrospective study; risk factor; body mass; immunotherapy; blood sampling; liver tumor; bile duct carcinoma; tumor; drug therapy; therapy; procedures; radioembolization; immune checkpoint inhibitor; cancer prognosis; nivolumab; very elderly; humans; human; male; female; article; pembrolizumab; durvalumab; immune checkpoint inhibitors; atezolizumab; ecog performance status |
| Journal Title: | The Oncologist |
| Volume: | 29 |
| Issue: | 10 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2024-10-01 |
| Start Page: | 894 |
| End Page: | 903 |
| Language: | English |
| DOI: | 10.1093/oncolo/oyae110 |
| PUBMED: | 38937977 |
| PROVIDER: | scopus |
| PMCID: | PMC11448888 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: James J. Harding -- Source: Scopus |
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