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阿替利珠单抗联合贝伐珠单抗对比乐伐替尼用于 Child Pugh B 不可切除肝细胞癌患者的生存结局。

Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients.

机构信息

Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy.

Department of Oncology, IRCCS San Raffaele Hospital, Milan, Italy.

出版信息

J Cancer Res Clin Oncol. 2023 Aug;149(10):7565-7577. doi: 10.1007/s00432-023-04678-2. Epub 2023 Mar 28.

Abstract

INTRODUCTION

The best first-line treatment for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class B remains unknown. The aim of the present study was to perform a real-world analysis on a large sample of patients with unresectable HCC with CP B treated with atezolizumab plus bevacizumab Vs Lenvatinib.

METHODS

The study population included patients affected by advanced (BCLC-C) or intermediate (BCLC-B) HCC patients not suitable for locoregional therapies from both the Western and Eastern world (Italy, Germany, Republic of Korea and Japan), who received atezolizumab plus bevacizumab or Lenvatinib as first-line treatment. All the study population presented a CP class of B. The primary endpoint of the study was the overall survival (OS) of CP B patients treated with Lenvatinib compared to atezolizumab plus bevacizumab. Survival curves were estimated using the product-limit method of Kaplan-Meier. The role of stratification factors was analyzed with log-rank tests. Finally, an interaction test was performed for the main baseline clinical characteristics.

RESULTS

217 CP B HCC patients were enrolled in the study: 65 (30%) received atezolizumab plus bevacizumab, and 152 (70%) received lenvatinib. The mOS for patients receiving Lenvatinib was 13.8 months (95% CI: 11.6-16.0), compared to 8.2 months (95% CI 6.3-10.2) for patients receiving atezolizumab plus bevacizumab as first-line treatment (atezolizumab plus bevacizumab Vs Lenvatinib: HR 1.9, 95% CI 1.2-3.0, p = 0.0050). No statistically significant differences were highlighted in terms of mPFS. The multivariate analysis confirmed that patients receiving Lenvatinib as first-line treatment have a significantly longer OS compared to patients receiving atezolizumab plus bevacizumab (HR 2.01; 95% CI 1.29-3.25, p = 0.0023). By evaluating the cohort of patients who received atezolizumab plus bevacizumab, we found that Child B patients with ECOG PS 0, or BCLC B stage or ALBI grade 1 were those who had benefited from the treatment thus showing survival outcomes no significantly different compared to those receiving Lenvatinib.

CONCLUSION

The present study suggests for the first time a major benefit from Lenvatinib compared to atezolizumab plus bevacizumab in a large cohort of patients with CP B class HCC.

摘要

简介

对于伴有 Child-Pugh(CP)B 级的晚期肝细胞癌(HCC)患者,最佳一线治疗方案仍不明确。本研究旨在对大量不可切除 HCC 伴 CP B 级的患者进行真实世界分析,这些患者接受了阿替利珠单抗联合贝伐珠单抗与仑伐替尼治疗。

方法

研究人群包括来自西方和东方世界(意大利、德国、韩国和日本)的晚期(BCLC-C)或中期(BCLC-B)不适合局部区域治疗的 HCC 患者,他们接受了阿替利珠单抗联合贝伐珠单抗或仑伐替尼作为一线治疗。所有研究人群的 CP 分级均为 B 级。本研究的主要终点是 CP B 患者接受仑伐替尼治疗与阿替利珠单抗联合贝伐珠单抗治疗的总生存期(OS)。采用 Kaplan-Meier 乘积限法估计生存曲线。采用对数秩检验分析分层因素的作用。最后,对主要基线临床特征进行了交互检验。

结果

本研究共纳入 217 例 CP B HCC 患者:65 例(30%)接受了阿替利珠单抗联合贝伐珠单抗治疗,152 例(70%)接受了仑伐替尼治疗。接受仑伐替尼治疗的患者中位 OS 为 13.8 个月(95%CI:11.6-16.0),而接受阿替利珠单抗联合贝伐珠单抗作为一线治疗的患者中位 OS 为 8.2 个月(95%CI:6.3-10.2)(阿替利珠单抗联合贝伐珠单抗与仑伐替尼相比:HR 1.9,95%CI 1.2-3.0,p=0.0050)。在中位无进展生存期(mPFS)方面,未观察到统计学显著差异。多变量分析证实,接受仑伐替尼作为一线治疗的患者与接受阿替利珠单抗联合贝伐珠单抗治疗的患者相比,OS 显著延长(HR 2.01;95%CI 1.29-3.25,p=0.0023)。通过评估接受阿替利珠单抗联合贝伐珠单抗治疗的患者队列,我们发现 ECOG PS 0、BCLC B 期或 ALBI 分级 1 的 Child B 患者从治疗中获益最大,其生存结局与接受仑伐替尼治疗的患者相比无显著差异。

结论

本研究首次表明,在大量 CP B 级 HCC 患者中,仑伐替尼与阿替利珠单抗联合贝伐珠单抗相比具有显著优势。

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