近日，美国加州大学洛杉矶分校Richard S. Finn与合作者团队探讨了阿妥珠单抗+贝伐珠单抗治疗无法切除的肝细胞癌的效果。2020年5月14日，《新英格兰医学杂志》发表了这项成果。

阿妥珠单抗联合贝伐珠单抗在临床1b期试验中显示了令人鼓舞的抗肿瘤活性和安全性，且涉及无法切除的肝细胞癌患者。

在这项全球性、开放标签的临床3期试验中，研究组招募了以前未接受过全身性治疗的无法切除的肝细胞癌患者，将其按2：1随机分组，其中336例接受阿妥珠单抗+贝伐珠单抗进行治疗，165例接受索拉非尼治疗，直至发生不可接受的毒性作用或失去临床获益。

在初步分析时，阿妥珠单抗+贝伐珠单抗组与索拉非尼组的死亡风险比为0.58，差异显著。阿妥珠单抗+贝伐珠单抗组在12个月时的总生存率为67.2%，而索拉非尼组为54.6%。阿妥珠单抗+贝伐珠单抗组的中位无进展生存期为6.8个月，显著长于索拉非尼组的4.3个月。

至少接受一剂阿妥珠单抗+贝伐珠单抗治疗的患者中有56.5%出现3级或4级不良事件，至少接受一剂索拉非尼治疗的患者中有55.1%。阿妥珠单抗+贝伐珠单抗组中有15.2％的患者发生3或4级高血压，但很少有其他更高级别的毒性作用。

综上，阿妥珠单抗联合贝伐珠单抗治疗无法切除的肝细胞癌患者，与索拉非尼相比，总体生存率和无进展生存率更高。

附：英文原文

Title: Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma

Author: Richard S. Finn, M.D.,, Shukui Qin, M.D.,, Masafumi Ikeda, M.D.,, Peter R. Galle, M.D.,, Michel Ducreux, M.D.,, Tae-You Kim, M.D.,, Masatoshi Kudo, M.D.,, Valeriy Breder, M.D.,, Philippe Merle, M.D.,, Ahmed O. Kaseb, M.D.,, Daneng Li, M.D.,, Wendy Verret, Ph.D.,, Derek-Zhen Xu, M.D.,, Sairy Hernandez, Ph.D.,, Juan Liu, Ph.D.,, Chen Huang, M.D.,, Sohail Mulla, Ph.D.,, Yulei Wang, Ph.D.,, Ho Yeong Lim, M.D.,, Andrew X. Zhu, M.D., Ph.D.,, and Ann-Lii Cheng, M.D.

Issue&Volume: 2020-05-13

Abstract: Abstract

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.

DOI: NJ202005143822009

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1915745