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贝伐珠单抗联合阿替利珠单抗治疗肝细胞癌的疗效和安全性:法国多中心真实世界匹配研究的治疗预后及与酪氨酸激酶抑制剂的比较。

Outcomes and safety of atezolizumab plus bevacizumab in the treatment of hepatocellular carcinoma: treatment prognosis and comparison with tyrosine kinase inhibitors in a French multicenter matched real-life study.

机构信息

Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille.

Department of Gastroenterology and Hepatology, Hôpital Universitaire de l'Archet, Nice.

出版信息

Eur J Gastroenterol Hepatol. 2024 Nov 1;36(11):1329-1339. doi: 10.1097/MEG.0000000000002830. Epub 2024 Jul 26.

Abstract

BACKGROUND AND AIMS

The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs).

METHODOLOGY

A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort ( n  = 79) by the propensity score matching method.

RESULTS

The Atz/Bev population was mainly nonviral disease patients (69%) with Child-Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6-11.7), overall survival (OS) was 13.0 (5.1-28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev.

CONCLUSION

This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.

摘要

背景与目的

阿替利珠单抗联合贝伐珠单抗(Atz/Bev)的联合治疗方案彻底改变了晚期肝细胞癌(HCC)的治疗策略,但也引发了一些疑问。我们的目的是在法国多中心真实世界队列中确定患者的生存结局和安全性,研究治疗过程中生物炎症 RECA 评分的预后价值,并与之前接受酪氨酸激酶抑制剂(TKI)治疗的患者进行匹配比较。

方法

回顾性分析了 2020 年 9 月至 2023 年 1 月期间入组的 109 例连续患者,并采用倾向评分匹配法与 TKI 队列(n=79)进行了匹配后比较。

结果

Atz/Bev 人群主要为非病毒性疾病患者(69%),Child-Pugh 分级为 A(90%),表现状态为 0/1(90%),巴塞罗那临床肝癌分期为 B(38%)或 C(62%)。中位随访 6.5 个月(3.6-11.7)后,总生存期(OS)为 13.0(5.1-28.7)个月。OS 与转移、碱性磷酸酶和血清胆红素水平升高独立相关。78%的患者报告了治疗相关的不良事件,大多为 1 级或 2 级。在三个周期后,RECA 评分清楚地显示了两个不同的预后组。在 TKI 和 Atz/Bev 序贯治疗之间进行匹配后,OS 无差异。

结论

本真实世界研究强调了在使用 Atz/Bev 联合治疗时肝功能的重要性,以及识别 HCC 治疗反应预测标志物的必要性。我们的研究结果表明,治疗实践发生了变化,中间阶段明显增多,支持炎症评分在治疗过程中的预后价值。

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