Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial.

Abstract

PURPOSE:

To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib.

METHODS:

A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response.

RESULTS:

Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9-8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2-4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22-7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02-4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011).

CONCLUSION:

IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.

• Authors: Osman Öcal, Kerstin Schütte, Juozas Kupčinskas, Egidijus Morkunas, Gabija Jurkeviciute, Enrico N de Toni, Najib Ben Khaled, Thomas Berg, Peter Malfertheiner, Heinz Josef Klümpen, Christian Sengel, Bristi Basu, Juan W Valle, Julia Benckert, Antonio Gasbarrini, Daniel Palmer, Ricarda Seidensticker, Moritz Wildgruber, Bruno Sangro, Maciej Pech, Jens Ricke, Max Seidensticker
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 148 Issue 2 Pg. 475-485 (Feb 2022) ISSN: 1432-1335 [Electronic] Germany
• PMID: 33855585 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2021. The Author(s).

Chemical References

• Interleukin-6
• Interleukin-8
• Sorafenib

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Hepatocellular (diagnosis, drug therapy, mortality, pathology)
• Disease Progression
• Europe (epidemiology)
• Female
• Follow-Up Studies
• Humans
• Interleukin-6 (blood)
• Interleukin-8 (blood)
• Liver Neoplasms (diagnosis, drug therapy, mortality, pathology)
• Male
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Sorafenib (therapeutic use)
• Survival Analysis
• Turkey (epidemiology)
• Young Adult