Supplementary Material for: The effectiveness of Long-Term Continuation of Atezolizumab Plus Bevacizumab In Patients Who Receiving Systemic Chemotherapy For Advanced Hepatocellular Carcinoma: A Multicenter Study

Introduction: Changes in liver function in patients with unresectable hepatocellular
carcinoma (u-HCC), following extended periods from the initiation of atezolizumab plus　
bevacizumab (Atez/Bev), have not been fully investigated.
Methods: Of 148 u-HCC patients treated with first-line Atez/Bev, the study enrolled 38 u-HCC
patients treated with first-line Atez/Bev, whose treatment response was initially evaluated as
non-progressive disease (non-PD) and later as PD on imaging, and who then received second-
line systemic chemotherapy. We evaluated the relationship between the period from the
initiation of first-line Atez/Bev to that of second-line systemic chemotherapy with liver
function and prognosis.
Results: According to the periods from the initiation of Atez/Bev to that of the second-line therapy, patients were classified into a long continuation group (Group-L, n = 19), ≥ 11 months; or a short continuation group (Group-S, n = 19), < 11 months. The albumin-bilirubin (ALBI) score at the initiation of the second-line therapy did not differ significantly between the groups (median: -2.38 vs. -2.02, P = 0.559), and the change in ALBI score also did not differ significantly between the groups (median: 0.42 vs. 0.51, P = 0.770). Group-L had significantly better overall survival (OS) than Group-S (not reached vs. 18 months, P = 0.008).
Conclusions: Liver function did not decrease even after long-term treatment with first-line Atez/Bev in patients who were able to progress to second-line therapy, indicating that long continuation of first-line Atez/Bev may be valuable for improving OS.

引言：接受阿替利珠单抗联合贝伐珠单抗（atezolizumab plus bevacizumab, Atez/Bev）长期治疗后，不可切除肝细胞癌（unresectable hepatocellular carcinoma, u-HCC）患者的肝功能变化尚未得到充分研究。
方法：在148例接受一线Atez/Bev治疗的u-HCC患者中，本研究纳入38例符合以下条件的患者：一线接受Atez/Bev治疗、初始影像学评估为非进展性疾病（non-progressive disease, non-PD）、后续影像学证实进展为进展性疾病（progressive disease, PD）并接受二线全身化疗。本研究评估了从一线Atez/Bev启动至二线全身化疗启动的间隔时长与肝功能及预后的相关性。
结果：根据从一线Atez/Bev启动至二线治疗启动的间隔时长，将患者分为长疗程组（L组，n=19，间隔≥11个月）与短疗程组（S组，n=19，间隔<11个月）。二线治疗启动时的白蛋白-胆红素（albumin-bilirubin, ALBI）评分在两组间无显著差异（中位数：-2.38 vs -2.02，P=0.559），ALBI评分的变化幅度同样无显著组间差异（中位数：0.42 vs 0.51，P=0.770）。L组的总生存期（overall survival, OS）显著优于S组（未达到vs 18个月，P=0.008）。
结论：对于能够进展至二线治疗的患者，即使接受长期一线Atez/Bev治疗，其肝功能也未出现下降，提示延长一线Atez/Bev治疗时长或可改善患者总生存期。