Supplementary Material for: The Neutrophil-to-Lymphocyte Ratio during Atezolizumab plus Bevacizumab Therapy for Unresectable Hepatocellular Carcinoma Predicts Long-term Therapeutic Efficacy: A Multicenter Analysis

Introduction: Atezolizumab plus bevacizumab (ATZ/BEV) is used for the treatment of unresectable hepatocellular carcinoma (u-HCC). However, there are few reports investigating the predictors of whether or not disease control can be achieved for long periods. Methods: We enrolled 106 u-HCC patients who were treated with ATZ/BEV as the first-line systemic chemotherapy and were evaluated as non-progressive disease (non-PD) in their initial assessments. They were divided into two groups: patients who had achieved disease control (non-PD) for more than 6 months, Group-L, and patients who had progressed (PD) within 6 months, Group-S. We investigated the predictors of long-term therapeutic efficacy. Results: Patients in Group-L had significantly lower neutrophil-to-lymphocyte ratios (NLR) (the ratios of NLR at the start of the second course of ATZ/BEV to their pretreatment levels) than Group-S (P = 0.044), and the optimal cut-off value was 1.129. The patients with an NLR ratio <1.129 had longer progression-free survival (PFS) and overall survival (OS) than those with an NLR ratio ≥1.129 (median: 16 vs. 6 months, P = 0.016 for PFS; not reached vs. 22 months, P = 0.007 for OS). Univariate and multivariate analyses showed that an NLR ratio ≥1.129 was an independent predictor for unfavorable PFS and OS (hazard ratio [HR] 2.03, P = 0.022 for PFS; HR 2.37, P = 0.019 for OS). Conclusions: In u-HCC patients treated with ATZ/BEV, a lower NLR ratio was associated with a durable response, which led to favorable PFS and OS.