Kudo Masatoshi, Finn Richard S, Galle Peter R, Zhu Andrew X, Ducreux Michel, Cheng Ann-Lii, Ikeda Masafumi, Tsuchiya Kaoru, Aoki Ken-Ichi, Jia Jing, Lencioni Riccardo
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
Department of Medicine, Division of Hematology and Oncology, Jonsson Comprehensive Cancer Center, Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Liver Cancer. 2022 Nov 28;12(3):238-250. doi: 10.1159/000528272. eCollection 2023 Aug.
The phase III IMbrave150 study established atezolizumab + bevacizumab as standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis reports efficacy and safety results in patients with baseline Barcelona Clinic Liver Cancer (BCLC) stage B disease.
Patients with systemic treatment-naive unresectable HCC and Child-Pugh class A liver function were randomized 2:1 to receive 1,200 mg of atezolizumab plus 15 mg/kg of bevacizumab or 400 mg of sorafenib. Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in the BCLC stage B subgroup. Patients in this analysis had BCLC stage B disease at baseline per electronic case report form. Secondary efficacy endpoints included the objective response rate (ORR) and change in the sum of longest diameters (SLD) of target lesions from baseline per IRF RECIST 1.1 and modified RECIST (mRECIST) for HCC.
Of 501 enrolled patients, 74 (15%) had BCLC stage B disease at baseline (atezolizumab + bevacizumab, = 49; sorafenib, = 24). For this group, median follow-up was 19.7 months. A trend toward improved OS and PFS per IRF RECIST 1.1 was observed with atezolizumab + bevacizumab versus sorafenib (OS: hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.29, 1.34; PFS: HR: 0.64; 95% CI: 0.36, 1.12). ORRs per IRF RECIST 1.1 and HCC mRECIST were 43% and 50% with atezolizumab + bevacizumab and 26% and 30% with sorafenib, respectively. Percentage change in SLD of target lesions from baseline per IRF RECIST 1.1 and HCC mRECIST showed durable responses with atezolizumab + bevacizumab treatment. Safety data were consistent with known profiles of atezolizumab and bevacizumab, as seen in the overall study population.
DISCUSSION/CONCLUSION: Efficacy benefits were observed with atezolizumab + bevacizumab in patients with baseline BCLC stage B disease, consistent with the intention-to-treat population.
III期IMbrave150研究确立了阿替利珠单抗+贝伐珠单抗作为不可切除肝细胞癌（HCC）患者的标准治疗方案。本探索性分析报告了基线巴塞罗那临床肝癌（BCLC）分期为B期疾病患者的疗效和安全性结果。
未接受过全身治疗的不可切除HCC且肝功能为Child-Pugh A级的患者按2:1随机分组，分别接受1200mg阿替利珠单抗加15mg/kg贝伐珠单抗或400mg索拉非尼治疗。共同主要终点是根据独立审查机构（IRF）评估的实体瘤疗效评价标准（RECIST）1.1版，BCLC B期亚组的总生存期（OS）和无进展生存期（PFS）。该分析中的患者根据电子病例报告表在基线时为BCLC B期疾病。次要疗效终点包括根据IRF RECIST 1.1和HCC改良RECIST（mRECIST）标准评估的客观缓解率（ORR）以及靶病灶最长径总和（SLD）较基线的变化。
在501例入组患者中，74例（15%）在基线时为BCLC B期疾病（阿替利珠单抗+贝伐珠单抗组，n = 49；索拉非尼组，n = 24）。该组的中位随访时间为19.7个月。与索拉非尼相比，阿替利珠单抗+贝伐珠单抗组根据IRF RECIST 1.1标准观察到OS和PFS有改善趋势（OS：风险比[HR]：0.63；95%置信区间[CI]：0.29，1.34；PFS：HR：0.64；95%CI：0.36，1.12）。根据IRF RECIST 1.1标准和HCC mRECIST标准，阿替利珠单抗+贝伐珠单抗组的ORR分别为43%和50%，索拉非尼组分别为26%和30%。根据IRF RECIST 1.1标准和HCC mRECIST标准，靶病灶SLD较基线的百分比变化显示阿替利珠单抗+贝伐珠单抗治疗有持久反应。安全性数据与整个研究人群中阿替利珠单抗和贝伐珠单抗已知的特征一致。
讨论/结论：在基线BCLC B期疾病患者中观察到阿替利珠单抗+贝伐珠单抗有疗效获益，与意向性治疗人群一致。
