Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Liver Int. 2024 Apr;44(4):907-919. doi: 10.1111/liv.15826. Epub 2024 Jan 30.
BACKGROUND & AIMS: Tumour microenvironment heterogeneity among different organs can influence immunotherapy responses. Here, we evaluated the impact of differential organ-specific responses on survival in patients with advanced-stage hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atezo/Bev).
We retrospectively analysed 366 consecutive patients with advanced-stage HCC treated with Atezo/Bev as first-line systemic treatment. Therapeutic response was assessed using RECIST v1.1. Patients were divided into an intention-to-treat (ITT) group (patients treated with ≥1 dose of Atezo/Bev) and a per-protocol (PP) analysis group (patients with at least one measurable lesion irrespective of location treated with ≥3 doses of Atezo/Bev). Overall response and organ-specific response at initial and best response were evaluated in the PP group. Responders were defined as patients achieving complete remission or partial response. Initial progressors were defined as patients with progressive disease after three doses of Atezo/Bev.
The ITT and PP groups comprised 324 and 236 patients, respectively. In the PP group, the organ-specific response rate of lung and lymph node (LN) metastases at both initial and best responses were higher than those of intrahepatic lesions and macrovascular tumour thrombosis. Lung and LN-specific response rates were 21.1% and 23.5%, respectively, at initial response, and 24.7% and 31.4%, respectively, at best response. Both initial pulmonary and lymphatic progressors (adjusted hazard ratios [95% confidence intervals], 6.37 [2.10-19.3], and 8.36 [2.16-32.4], respectively) were independently associated with survival regardless of intrahepatic response.
The response of metastatic HCC to the Atezo/Bev regimen may be used to determine whether to continue treatment or switch to second-line treatment at an early phase of therapy.
不同器官的肿瘤微环境异质性可能影响免疫治疗反应。在此，我们评估了在接受阿替利珠单抗联合贝伐珠单抗（Atezo/Bev）治疗的晚期肝细胞癌（HCC）患者中，器官特异性反应差异对生存的影响。
我们回顾性分析了 366 例接受 Atezo/Bev 作为一线系统治疗的晚期 HCC 患者。采用 RECIST v1.1 评估治疗反应。患者分为意向治疗（ITT）组（接受≥1 剂 Atezo/Bev 治疗的患者）和方案治疗（PP）分析组（接受≥3 剂 Atezo/Bev 治疗的至少有一个可测量病变且不论位置的患者）。在 PP 组中评估初始和最佳反应时的总体反应和器官特异性反应。应答者定义为完全缓解或部分缓解的患者。初始进展者定义为接受 Atezo/Bev 治疗 3 剂后出现疾病进展的患者。
ITT 组和 PP 组分别纳入 324 例和 236 例患者。在 PP 组中，肺和淋巴结（LN）转移的初始和最佳反应的器官特异性反应率均高于肝内病变和大血管肿瘤血栓。初始反应时肺和 LN 特异性反应率分别为 21.1%和 23.5%，最佳反应时分别为 24.7%和 31.4%。初始肺部和淋巴进展者（调整后的危险比[95%置信区间]，6.37[2.10-19.3]和 8.36[2.16-32.4]）均与生存独立相关，而与肝内反应无关。
转移性 HCC 对 Atezo/Bev 方案的反应可用于确定在治疗早期是否继续治疗或切换至二线治疗。
