Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany.
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, Germany.
Aliment Pharmacol Ther. 2023 Jun;57(11):1313-1325. doi: 10.1111/apt.17441. Epub 2023 Mar 8.
Phase III trials have established atezolizumab plus bevacizumab as the novel standard of care for patients with unresectable hepatocellular carcinoma (HCC). However, these trials raised concerns regarding treatment efficacy in non-viral HCC, and it remains unclear whether combination immunotherapy is safe and effective in patients with advanced cirrhosis.
One hundred patients with unresectable HCC initiated therapy with atezolizumab plus bevacizumab at our centre between January 2020 and March 2022. The control cohort consisted of 80 patients with advanced HCC who received either sorafenib (n = 43) or lenvatinib (n = 37) as systemic treatment.
Overall survival (OS) and progression-free survival (PFS) were significantly longer within the atezolizumab/bevacizumab group and comparable to phase III data. The benefits in terms of increased objective response rate (ORR), OS and PFS were consistent across subgroups, including non-viral HCC (58%). The ROC-optimised neutrophil-to-lymphocyte ratio (NLR) cut-off of 3.20 was the strongest independent predictor of ORR and PFS. In patients with advanced cirrhosis Child-Pugh B, liver function was significantly better preserved with immunotherapy. Patients with Child-Pugh B cirrhosis showed similar ORR but shorter OS and PFS compared to patients with preserved liver function.
Atezolizumab plus bevacizumab showed good efficacy and safety in patients with unresectable HCC and partially advanced liver cirrhosis in a real-world setting. Moreover, the NLR was able to predict response to atezolizumab/bevacizumab treatment and may guide patient selection.
III 期临床试验已经确立了阿替利珠单抗联合贝伐珠单抗作为不可切除肝细胞癌(HCC)患者的新型标准治疗方法。然而,这些试验引起了人们对非病毒性 HCC 治疗效果的关注,并且尚不清楚联合免疫疗法在晚期肝硬化患者中是否安全有效。
2020 年 1 月至 2022 年 3 月期间,我们中心有 100 名不可切除 HCC 患者开始接受阿替利珠单抗联合贝伐珠单抗治疗。对照组由 80 名接受索拉非尼(n=43)或仑伐替尼(n=37)系统治疗的晚期 HCC 患者组成。
阿替利珠单抗/贝伐珠单抗组的总生存期(OS)和无进展生存期(PFS)明显更长,与 III 期数据相当。在增加客观缓解率(ORR)、OS 和 PFS 方面,该获益在亚组中是一致的,包括非病毒性 HCC(58%)。ROC 优化的中性粒细胞与淋巴细胞比值(NLR)截断值 3.20 是 ORR 和 PFS 的最强独立预测因子。在 Child-Pugh B 级的晚期肝硬化患者中,免疫治疗显著改善了肝功能。Child-Pugh B 级肝硬化患者的 ORR 相似,但 OS 和 PFS 短于肝功能正常的患者。
在真实世界环境中,阿替利珠单抗联合贝伐珠单抗在不可切除 HCC 和部分晚期肝硬化患者中显示出良好的疗效和安全性。此外,NLR 能够预测阿替利珠单抗/贝伐珠单抗治疗的反应,可能有助于指导患者选择。