Serum interleukin‐6 levels at the start of the second course of atezolizumab plus bevacizumab therapy predict therapeutic efficacy in patients with advanced hepatocellular carcinoma: a multicenter analysis

Abstract Background and Aim Serum interleukin‐6 (IL‐6) before the administration of atezolizumab plus bevacizumab (Atez + Bev) is a prognostic biomarker in patients with hepatocellular carcinoma (HCC) treated with Atez + Bev. We previously revealed that the neutrophil‐to‐lymphocyte ratio and serum chemokine levels during treatment with Atez + Bev were more useful as prognostic biomarkers. Therefore, we examined the predictive ability of serum IL‐6 for the efficacy of Atez + Bev in patients with HCC. Methods We enrolled 94 patients with HCC who received treatment with Atez + Bev. Initial responses were assessed through dynamic computed tomography or magnetic resonance imaging. The levels of IL‐6 in serum were measured before and at the initiation of the second course of Atez + Bev. Subsequently, the relationship of IL‐6 levels with treatment efficacy was evaluated. Results IL‐6 levels at the initiation of the second course tended to be higher in patients with progressive disease versus those with non‐progressive disease in the initial evaluation ( P = 0.054). Moreover, the cutoff value (7.4 pg/mL) was useful in stratifying patients by overall survival (i.e. low vs high: not reached vs 21.4 months, respectively, P = 0.001) and progression‐free survival (low vs high: 11.9 vs 5.2 months, respectively, P = 0.004). This result was reproduced in patients with HCC who received Atez + Bev as first‐line therapy. In the multivariate analyses, IL‐6 levels at the initiation of the second course were independent predictive factors for progression‐free and overall survival. Conclusions Serum levels of IL‐6 at the initiation of the second course of treatment may predict Atez + Bev efficacy and prognosis in HCC.