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
Osman Öcal 1 , Kerstin Schütte 2 , Juozas Kupčinskas 3 , Egidijus Morkunas 3 , Gabija Jurkeviciute 3 , Enrico N de Toni 4 , Najib Ben Khaled 4 , Thomas Berg 5 , Peter Malfertheiner 4 , Heinz Josef Klümpen 6 , Christian Sengel 7 , Bristi Basu 8 , Juan W Valle 9 , Julia Benckert 10 , Antonio Gasbarrini 11 , Daniel Palmer 12 , Ricarda Seidensticker 1 , Moritz Wildgruber 1 , Bruno Sangro 13 , Maciej Pech 14 , Jens Ricke 1 , Max Seidensticker 15
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.
CITA DEL ARTÍCULO J Cancer Res Clin Oncol. 2022 Feb;148(2):475-485. doi: 10.1007/s00432-021-03627-1. Epub 2021 Apr 14.