阿替利珠单抗联合贝伐单抗与索拉非尼治疗IMbrave150研究中存在主干和/或对侧门静脉侵犯的肝细胞癌的疗效和安全性
Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma with Main Trunk and/or Contralateral Portal Vein Invasion in IMbrave150.
作者信息
Finn Richard S, Galle Peter R, Ducreux Michel, Cheng Ann-Lii, Reilly Norelle, Nicholas Alan, Hernandez Sairy, Ma Ning, Merle Philippe, Salem Riad, Li Daneng, Breder Valeriy
机构信息
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
University Medical Center Mainz, Mainz, Germany.
出版信息
Liver Cancer. 2024 Jun 21;13(6):655-668. doi: 10.1159/000539897. eCollection 2024 Dec.
INTRODUCTION
Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety in patient subpopulations with Vp4 portal vein tumor thrombosis (PVTT) and other high-risk prognostic factors are reported.
METHODS
IMbrave150 was a global, randomized (2:1), open-label, phase 3 study in systemic treatment-naive patients with unresectable HCC; OS and PFS were co-primary endpoints. Exploratory analyses compared the efficacy and safety of atezolizumab 1,200 mg plus bevacizumab 15 mg/kg every 3 weeks versus sorafenib 400 mg twice daily in patients (i) with and without Vp4 PVTT alone and (ii) with and without high-risk prognostic factors.
RESULTS
In patients with Vp4 PVTT, median OS was 7.6 months (95% CI: 6.0-13.9) with atezolizumab plus bevacizumab ( = 48) and 5.5 months (95% CI: 3.4-6.7) with sorafenib ( = 25; HR 0.62 [95% CI: 0.34-1.11]; descriptive = 0.104). Median PFS in the respective arms was 5.4 months (95% CI: 3.6-6.9) and 2.8 months (95% CI: 1.5-5.3; HR 0.62 [95% CI: 0.35-1.09]; descriptive = 0.094). In patients without Vp4, median OS was 21.1 months (95% CI: 18.0-24.6) with atezolizumab plus bevacizumab ( = 288) and 15.4 months (95% CI: 12.6-18.6) with sorafenib ( = 140; HR 0.67 [95% CI: 0.51-0.88]; descriptive = 0.003). Median PFS in the respective arms was 7.1 months (95% CI: 6.1-9.6) and 4.7 months (95% CI: 4.2-6.1; HR 0.64 [95% CI: 0.51-0.81]; descriptive < 0.001). The high-risk versus non-high-risk populations had similar outcome patterns. In the respective treatment arms, grade ≥3 treatment-related adverse events occurred in 43% and 48% of patients with Vp4 and 46% and 47% of patients without Vp4.
CONCLUSION
Regardless of VP4 PVTT or other high-risk features of unresectable HCC, which have often resulted in exclusion from other front-line trials, patients benefited from atezolizumab and bevacizumab versus sorafenib.
引言
在IMbrave150研究中，与索拉非尼相比，阿替利珠单抗联合贝伐珠单抗显著改善了不可切除肝细胞癌（HCC）患者的总生存期（OS）和无进展生存期（PFS）。报告了伴有Vp4门静脉肿瘤血栓形成（PVTT）和其他高危预后因素的患者亚群的疗效和安全性。
方法
IMbrave150是一项针对未经系统治疗的不可切除HCC患者的全球、随机（2:1）、开放标签的3期研究；OS和PFS为共同主要终点。探索性分析比较了每3周一次使用1200mg阿替利珠单抗联合15mg/kg贝伐珠单抗与每日两次使用400mg索拉非尼，在（i）单独伴有和不伴有Vp4 PVTT的患者以及（ii）伴有和不伴有高危预后因素的患者中的疗效和安全性。
结果
在伴有Vp4 PVTT的患者中，阿替利珠单抗联合贝伐珠单抗组的中位OS为7.6个月（95%CI：6.0 - 13.9）（n = 48），索拉非尼组为5.5个月（95%CI：3.4 - 6.7）（n = 25；HR 0.62 [95%CI：0.34 - 1.11]；描述性P = 0.104）。各治疗组的中位PFS分别为5.4个月（95%CI：3.6 - 6.9）和2.8个月（95%CI：1.5 - 5.3；HR 0.62 [95%CI：0.35 - 1.09]；描述性P = 0.094）。在不伴有Vp4的患者中，阿替利珠单抗联合贝伐珠单抗组的中位OS为21.1个月（95%CI：18.0 - 24.6）（n = 288），索拉非尼组为15.4个月（95%CI：12.6 - 18.6）（n = 140；HR 0.67 [95%CI：0.51 - 0.88]；描述性P = 0.003）。各治疗组的中位PFS分别为7.1个月（95%CI：6.1 - 9.6）和4.7个月（95%CI：4.2 - 6.1；HR 0.64 [95%CI：0.51 - 0.81]；描述性P < 0.001）。高危人群与非高危人群具有相似的结果模式。在各治疗组中，Vp4患者中分别有43%和48%、非Vp4患者中分别有46%和47%发生了≥3级治疗相关不良事件。
结论
无论不可切除HCC的Vp4 PVTT或其他高危特征如何（这些特征常导致被排除在其他一线试验之外），与索拉非尼相比，患者使用阿替利珠单抗和贝伐珠单抗均能获益。
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