Introduction The phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. Results Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. Discussion/Conclusion Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab.

中文翻译：

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由于贝伐单抗对接受 Atezolizumab 加贝伐单抗治疗的不可切除肝细胞癌患者特别关注的不良事件而被跳过贝伐单抗的影响：III 期 IMbrave150 研究的探索性分析。


简介 III 期 IMbrave150 研究将 atezolizumab + 贝伐单抗确立为不可切除肝细胞癌 (HCC) 患者的全球护理标准。这项探索性分析检查了因贝伐珠单抗特殊关注不良事件 (AESI) 导致贝伐珠单抗中断的影响。方法 IMbrave150 中被随机分配至 atezolizumab + 贝伐单抗并接受治疗 ≥ 6 个月（以减少永生时间偏差）的患者，如果曾因贝伐单抗 ASI 而跳过贝伐单抗，则被纳入 A-1 组，否则被纳入 A-2 组。疗效分析包括根据是否跳过贝伐珠单抗的总生存期 (OS) 和无进展生存期 (PFS)（A-1 组与 A-2 组）。 PFS 根据独立审查机构 (IRF) 评估的实体瘤疗效评估标准 (RECIST) 1.1 版和 HCC 修订的 RECIST (IRF-HCC mRECIST) 进行评估。还评估了安全性。结果 在接受 atezolizumab + 贝伐珠单抗≥6 个月的 210 名患者中，69 名被分配到 A-1 组，141 名被分配到 A-2 组。截至数据截止时（2020 年 8 月 20 日），A-1 组与 A-2 组的 OS 风险比 (HR) 为 1.04（95% CI：0.64，1.69）。根据 IRF-HCC mRECIST，A-1 组与 A-组的 PFS HR 为 1.07（95% CI：0.74, 1.55），根据 IRF 评估的 RECIST 1.1 和 1.10（95% CI：0.76, 1.59；15.5 与 9.7 个月） 2.阿特朱单抗和贝伐单抗的安全性在各组之间基本相似。更多 A-1 组患者出现 3/4 级不良事件。另一项独立分析调查了接受 ≥3 个月阿特珠单抗 + 贝伐珠单抗治疗的患者的永生时间偏差的影响，支持了 ≥6 个月里程碑分析的适当性。讨论/结论 由于贝伐单抗 AESI 而跳过贝伐单抗的患者与未跳过贝伐单抗的患者的疗效相似。 尽管这一比较是非随机的和探索性的，但结果表明，由于贝伐单抗 AESI 而跳过贝伐单抗并没有显着影响阿特珠单抗 + 贝伐单抗的疗效和安全性。