No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice–web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with , . The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9–22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1–NE]) compared with active surveillance (median, NE [21·4–NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53–0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab. Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit–risk profile more fully. F Hoffmann-La Roche/Genentech.

中文翻译：

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Atezolizumab 加贝伐单抗与已切除或消融的高危肝细胞癌患者的主动监测 (IMbrave050)：一项随机、开放标签、多中心、3 期试验

对于根治性切除或消融后仍处于肝细胞癌复发高风险的患者，尚未建立辅助治疗方法。我们的目的是评估阿特珠单抗联合贝伐珠单抗辅助治疗与主动监测对高危肝细胞癌患者的疗效。在全球开放标签 3 期 IMbrave050 研究中，从 WHO 四个区域（欧洲区域、美洲区域、南美洲区域）的 26 个国家的 134 家医院和医疗中心招募了高危手术切除或消融性肝细胞癌成年患者。 -东亚地区、西太平洋地区）。通过使用排列块的交互式语音网络应答系统，将患者以 1:1 的比例随机分配，使用块大小为 4，每 3 周接受静脉注射 1200 mg 阿替利珠单抗加 15 mg/kg 贝伐珠单抗，共 17 个周期（12 个月） ）或主动监视。主要终点是通过独立审查机构对意向治疗人群进行评估得出的无复发生存率。该试验已在 , 注册。意向治疗人群包括 668 名患者，在 2019 年 12 月 31 日至 2021 年 11 月 25 日期间被随机分配至阿替珠单抗加贝伐单抗组 (n=334) 或主动监测组 (n=334)。在预先指定的中期分析（2022 年 10 月 21 日）中，中位随访时间为 17·4 个月（IQR 13·9–22·1）。与主动监测（中位，NE [21·4-NE]）相比，辅助阿特珠单抗联合贝伐珠单抗可显着改善无复发生存期（中位，不可评估 [NE]；[95% CI 22·1-NE]）。比，0·72 [调整后的 95% CI 0·53–0·98]；p=0·012）。接受阿特珠单抗联合贝伐珠单抗治疗的 332 名患者中有 136 名（41%）发生了 3 级或 4 级不良事件，主动监测组的 330 名患者中有 44 名（13%）发生了 3 级或 4 级不良事件。阿特珠单抗联合贝伐珠单抗组中有 6 名患者（2%，其中两名与治疗相关）发生了 5 级不良事件，主动监测组有 1 名患者（<1%）发生了 5 级不良事件。阿特珠单抗和贝伐珠单抗均因 29 名接受阿特珠单抗联合贝伐珠单抗治疗的患者 (9%) 发生不良事件而停药。在根治性切除或消融后肝细胞癌复发高风险的患者中，与主动监测相比，接受阿特珠单抗联合贝伐珠单抗治疗的患者无复发生存期有所改善。据我们所知，IMbrave050是第一个报告阳性结果的肝细胞癌辅助治疗3期研究。然而，需要对无复发生存期和总生存期进行更长时间的随访，以更全面地评估获益-风险状况。F 霍夫曼-拉罗氏/基因泰克。