阿替利珠单抗联合贝伐珠单抗治疗不可切除肝细胞癌。
Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma.
机构信息
From the Jonsson Comprehensive Cancer Center, Geffen School of Medicine at UCLA, Los Angeles (R.S.F.), the City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte (D.L.), and Genentech, South San Francisco (W.V., S.H., Y.W.) - all in California; the People's Liberation Army Cancer Center, Jinling Hospital, Nanjing (S.Q.), and Roche Product Development (D.-Z.X., J.L., C.H.) and Jiahui International Cancer Center, Jiahui Health (A.X.Z.), Shanghai - all in China; National Cancer Center Hospital East, Kashiwa (M.I.), and Kindai University Faculty of Medicine, Osaka (M.K.) - both in Japan; University Medical Center Mainz, Mainz, Germany (P.R.G.); Gustave Roussy Cancer Center, Paris-Saclay University, Villejuif (M.D.), and University Hospital La Croix-Rousse, Lyon (P.M.) - both in France; Seoul National University College of Medicine (T.-Y.K.) and Samsung Medical Center, Sungkyunkwan University School of Medicine (H.Y.L.) - both in Seoul, South Korea; N.N. Blokhin Russian Cancer Research Center, Moscow (V.B.); the University of Texas M.D. Anderson Cancer Center, Houston (A.O.K.); Hoffmann-La Roche, Mississauga, ON, Canada (S.M.); Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston (A.X.Z.); and the National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei (A.-L.C.).
出版信息
N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.
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.).
背景
在一项涉及不可切除肝细胞癌患者的 1b 期试验中，阿替利珠单抗联合贝伐珠单抗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、开放性、3 期试验中，未接受过系统治疗的不可切除肝细胞癌患者按 2:1 的比例随机分配，接受阿替利珠单抗联合贝伐珠单抗或索拉非尼治疗，直至出现不可接受的毒性作用或临床获益丧失。主要终点是在意向治疗人群中根据实体瘤反应评估标准 1.1（RECIST 1.1）评估的总生存期和无进展生存期。
结果
在意向治疗人群中，阿替利珠单抗联合贝伐珠单抗组有 336 例患者，索拉非尼组有 165 例患者。在主要分析时（2019 年 8 月 29 日），阿替利珠单抗联合贝伐珠单抗组的死亡风险比索拉非尼组低 58%（95%置信区间[CI]，42 至 79；P<0.001）。阿替利珠单抗联合贝伐珠单抗组的 12 个月总生存率为 67.2%（95%CI，61.3 至 73.1），索拉非尼组为 54.6%（95%CI，45.2 至 64.0）。两组的中位无进展生存期分别为 6.8 个月（95%CI，5.7 至 8.3）和 4.3 个月（95%CI，4.0 至 5.6）（疾病进展或死亡的风险比，0.59；95%CI，0.47 至 0.76；P<0.001）。329 例接受至少一剂阿替利珠单抗联合贝伐珠单抗治疗的患者中，56.5%发生了 3 级或 4 级不良事件，156 例接受至少一剂索拉非尼治疗的患者中，55.1%发生了 3 级或 4 级不良事件。阿替利珠单抗联合贝伐珠单抗组 15.2%的患者发生 3 级或 4 级高血压；然而，其他高级别毒性反应不常见。
结论
在不可切除肝细胞癌患者中，阿替利珠单抗联合贝伐珠单抗治疗的总生存期和无进展生存期优于索拉非尼。（由 F. Hoffmann-La Roche/Genentech 资助；ClinicalTrials.gov 编号，NCT03434379）。
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