阿替利珠单抗联合贝伐珠单抗治疗不可切除肝细胞癌患者的有效性和安全性：一项系统评价和荟萃分析

Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

作者信息

Kulkarni Anand V, Tevethia Harshvardhan, Kumar Karan, Premkumar Madhumita, Muttaiah Mark D, Hiraoka Atsushi, Hatanaka Takeshi, Tada Toshifumi, Kumada Takashi, Kakizaki Satoru, Vogel Arndt, Finn Richard S, Rao Padaki Nagaraja, Pillai Anjana, Reddy Duvvur Nageshwar, Singal Amit G

机构信息

Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India.

Department of Hepatology, ILBS, New Delhi, India.

出版信息

EClinicalMedicine. 2023 Aug 30;63:102179. doi: 10.1016/j.eclinm.2023.102179. eCollection 2023 Sep.

BACKGROUND

Atezolizumab-bevacizumab (atezo-bev) is recommended as first-line therapy for patients with unresectable hepatocellular carcinoma (uHCC). However, its effectiveness and safety in other populations, including those with Child-Turcotte-Pugh (CTP) class B cirrhosis, is unclear.

METHODS

For this systematic review and meta-analysis, electronic databases, including PubMed, Embase, and Scopus, were searched from 1st May, 2020 till 5th October, 2022; the last date of access was January 31, 2023. Pooled progression-free survival (PFS), overall survival (OS), and radiological response rate among patients receiving atezo-bev were compared between patients with CTP-A and CTP-B cirrhosis, with tyrosine kinase inhibitors (TKIs) and among those receiving the drug as first-line and later line therapy. The protocol was registered in Prospero (CRD42022364430).

FINDINGS

Among 47 studies (n = 5400 patients), pooled PFS and OS were 6.86 (95% CI, 6.31-7.41) and 13.8 months (95% CI, 11.81-15.8), respectively. Objective response rate (ORR) and disease control rate were 26.7% (24.6-29.1) and 75.3% (73.1-77.4) using RECIST criteria, and 34% (30.3-37.8) and 73.6% (68.8-78) using mRECIST criteria, respectively. Among those receiving atezo-bev, patients with CTP-B cirrhosis had similar ORRs by RECIST (odds ratio [OR], 1.42 [0.77-2.6]; P = 0.25) and mRECIST criteria (OR, 1.33 [0.52-3.39]; P = 0.53) but shorter PFS (mean difference [MD]:3.83 months [1.81-5.84]) than those with CTP-A cirrhosis. Compared to patients receiving TKIs, those receiving atezo-bev had longer PFS (MD: 2.27 months [0.94-3.5]) and higher ORR (RECIST: OR, 1.44 [1.01-2.04] and mRECIST: OR, 1.33 [1.01-1.75]). Compared to first-line therapy, later-line therapy had lower ORR (RECIST: OR, 1.82 [1.3-2.53]; P < 0.001 and mRECIST: OR, 2.02 [1.34-3.05]) but comparable PFS (MD: 0.58 months [-0.18 to 1.35]) among nine studies. The incidence of grade ≥3 adverse events among patients with CTP-A and CTP-B cirrhosis was comparable (OR, 0.89 [0.45-1.74]) as it was for patients receiving atezo-bev and TKIs (OR, 0.86 [0.61-1.2]).

INTERPRETATION

Our findings suggest that atezo-bev is safe and effective as first-line systemic therapy for patients with uHCC and CTP-A or CTP-B cirrhosis.

FUNDING

An unsolicited grant from ROCHE Products India Pvt Ltd. was received for publication.

背景

阿替利珠单抗-贝伐珠单抗（阿替利珠单抗联合贝伐珠单抗）被推荐作为不可切除肝细胞癌（uHCC）患者的一线治疗方案。然而，其在包括Child-Turcotte-Pugh（CTP）B级肝硬化患者在内的其他人群中的有效性和安全性尚不清楚。

方法

对于这项系统评价和荟萃分析，检索了电子数据库，包括PubMed、Embase和Scopus，检索时间从2020年5月1日至2022年10月5日；最后一次访问日期为2023年1月31日。比较了CTP-A级和CTP-B级肝硬化患者、接受酪氨酸激酶抑制剂（TKIs）治疗的患者以及接受该药物一线和二线治疗的患者中接受阿替利珠单抗联合贝伐珠单抗治疗患者的汇总无进展生存期（PFS）、总生存期（OS）和放射学缓解率。该方案已在国际前瞻性系统评价注册库（Prospero）中注册（注册号：CRD42022364430）。

结果

在47项研究（n = 5400例患者）中，汇总的PFS和OS分别为6.86个月（95%CI，6.31 - 7.41）和13.8个月（95%CI，11.81 - 15.8）。根据实体瘤疗效评价标准（RECIST），客观缓解率（ORR）和疾病控制率分别为26.7%（24.6 - 29.1）和75.3%（73.1 - 77.4）；根据改良RECIST标准（mRECIST），分别为34%（30.3 - 37.8）和73.6%（68.8 - 78）。在接受阿替利珠单抗联合贝伐珠单抗治疗的患者中，CTP-B级肝硬化患者根据RECIST标准（优势比[OR]，1.42[0.77 - 2.6]；P = 0.25）和mRECIST标准（OR，1.33[0.52 - 3.39]；P = 0.53）的ORR相似，但PFS短于CTP-A级肝硬化患者（平均差[MD]：3.83个月[1.81 - 5.84]）。与接受TKIs治疗的患者相比，接受阿替利珠单抗联合贝伐珠单抗治疗的患者PFS更长（MD：2.27个月[0.94 - 3.5]），ORR更高（RECIST标准：OR，1.44[1.01 - 2.04]；mRECIST标准：OR，1.33[1.01 - 1.75]）。与一线治疗相比，二线治疗的ORR较低（RECIST标准：OR，1.82[1.3 - 2.53]；P < 0.001；mRECIST标准：OR，2.02[1.34 - 3.05]），但在9项研究中PFS相当（MD：0.58个月[-0.18至1.35]）。CTP-A级和CTP-B级肝硬化患者中≥3级不良事件的发生率相当（OR，0.89[0.45 - 1.74]），接受阿替利珠单抗联合贝伐珠单抗治疗和接受TKIs治疗的患者也是如此（OR，0.86[0.61 - 1.2]）。