BACKGROUND The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma. METHODS In a global, open-label, phase 3 trial, patients with unresectable hepatocellular carcinoma who had not previously received systemic treatment were randomly assigned in a 2:1 ratio to receive either atezolizumab plus bevacizumab or sorafenib until unacceptable toxic effects occurred or there was a loss of clinical benefit. The coprimary end points were overall survival and progression-free survival in the intention-to-treat population, as assessed at an independent review facility according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). RESULTS The intention-to-treat population included 336 patients in the atezolizumab-bevacizumab group and 165 patients in the sorafenib group. At the time of the primary analysis (August 29, 2019), the hazard ratio for death with atezolizumab-bevacizumab as compared with sorafenib was 0.58 (95% confidence interval [CI], 0.42 to 0.79; P<0.001). Overall survival at 12 months was 67.2% (95% CI, 61.3 to 73.1) with atezolizumab-bevacizumab and 54.6% (95% CI, 45.2 to 64.0) with sorafenib. Median progression-free survival was 6.8 months (95% CI, 5.7 to 8.3) and 4.3 months (95% CI, 4.0 to 5.6) in the respective groups (hazard ratio for disease progression or death, 0.59; 95% CI, 0.47 to 0.76; P<0.001). Grade 3 or 4 adverse events occurred in 56.5% of 329 patients who received at least one dose of atezolizumab-bevacizumab and in 55.1% of 156 patients who received at least one dose of sorafenib. Grade 3 or 4 hypertension occurred in 15.2% of patients in the atezolizumab-bevacizumab group; however, other high-grade toxic effects were infrequent. CONCLUSIONS In patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT03434379.).

中文翻译：

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不可切除的肝细胞癌中的Atezolizumab加Bevacizumab。

背景技术在涉及无法切除的肝细胞癌患者的1b期临床试验中，atezolizumab和bevacizumab的组合显示出令人鼓舞的抗肿瘤活性和安全性。方法在一项全球性的，开放标签的3期试验中，以前未曾接受过全身性治疗的无法切除的肝细胞癌患者以2：1的比例随机分配，接受阿妥珠单抗加贝伐单抗或索拉非尼治疗，直至发生不可接受的毒性作用或出现失去临床利益。主要研究终点是意向性治疗人群的总体生存率和无进展生存期，这是根据独立的审查机构根据《实体肿瘤反应评估标准》 1.1版（RECIST 1.1）进行评估的结果。结果意向性治疗人群包括atezolizumab-bevacizumab组的336例患者和sorafenib组的165例患者。进行初步分析时（2019年8月29日），阿托珠单抗-贝伐单抗与索拉非尼的死亡危险比为0.58（95％置信区间[CI]，0.42至0.79; P <0.001）。Atezolizumab-bevacizumab在12个月时的总生存率为67.2％（95％CI，61.3至73.1），而索拉非尼则为54.6％（95％CI，45.2至64.0）。各个组的无进展中位生存期分别为6.8个月（95％CI，5.7至8.3）和4.3个月（95％CI，4.0至5.6）（疾病进展或死亡的危险比为0.59; 95％CI，0.47至0.76； P <0.001）。在接受至少一剂atezolizumab-bevacizumab的329例患者中，有56.5％发生了3或4级不良事件，其中55例发生了。接受至少一剂索拉非尼的156名患者中有1％。Atezolizumab-bevacizumab组中有15.2％的患者发生3级或4级高血压；然而，很少有其他高等级的毒性作用。结论在无法切除的肝细胞癌患者中，阿索唑单抗联合贝伐单抗比索拉非尼具有更好的总体生存率和无进展生存率。（由F. Hoffmann-La Roche / Genentech资助； ClinicalTrials.gov编号，NCT03434379。）。阿索唑单抗联合贝伐单抗比索拉非尼具有更好的总体生存率和无进展生存率。（由F. Hoffmann-La Roche / Genentech资助； ClinicalTrials.gov编号，NCT03434379。）。阿索唑单抗联合贝伐单抗比索拉非尼具有更好的总体生存率和无进展生存率。（由F. Hoffmann-La Roche / Genentech资助； ClinicalTrials.gov编号，NCT03434379。）。