不同 PD-1 抑制剂联合治疗不可切除的肝内胆管癌的效果。
Effect of different PD-1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma.
机构信息
Hepato-Pancreato-Biliary Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Department of Surgical Oncology, Qin Huai Medical District of Jinling Hospital, Nanjing University, Nanjing, China.
出版信息
Aliment Pharmacol Ther. 2023 Sep;58(6):611-622. doi: 10.1111/apt.17623. Epub 2023 Jun 22.
BACKGROUND
Immune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC).
AIM
To compare the effect of different anti-PD-1 combination therapies as the first-line treatments for uICC.
METHODS
This study included 318 patients who received chemotherapy alone (Chemo), anti-PD-1 plus chemotherapy (ICI-chemo), anti-PD-1 plus targeted therapy (ICI-target) or anti-PD-1 plus targeted therapy and chemotherapy (ICI-target-chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety.
RESULTS
Patients with ICI-chemo (median PFS [mPFS], 6.3 months; HR: 0.61, 95% CI: 0.42-0.88; p = 0.008; median OS [mOS], 10.7 months; HR: 0.61, 95% CI: 0.39-0.94; p = 0.026), ICI-target (7.2 months; HR: 0.54, 95% CI: 0.36-0.80; p = 0.002; 15.8 months; HR: 0.54, 95% CI: 0.35-0.84; p = 0.006) or ICI-target-chemo (6.9 months; HR: 0.65, 95% CI: 0.47-0.90; p = 0.009; 14.4 months; HR: 0.47, 95% CI: 0.31-0.70; p < 0.001) achieved better clinical outcomes than those with Chemo (3.8 months; 9.3 months). ICI-target was not inferior to ICI-chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55-1.42; p = 0.614; HR for OS: 0.89, 95% CI: 0.51-1.55; p = 0.680). ICI-target-chemo yielded similar prognoses as ICI-chemo (HR for PFS: 1.07, 95% CI: 0.70-1.62; p = 0.764; HR for OS: 0.77, 95% CI: 0.45-1.31; p = 0.328) and ICI-target (HR for PFS: 1.20, 95% CI: 0.77-1.88; p = 0.413; HR for OS: 0.86, 95% CI: 0.51-1.47; p = 0.583) but resulted in more adverse events (p < 0.001; p = 0.010). Multivariable and propensity score analyses supported these findings.
CONCLUSIONS
Among patients with uICC, ICI-chemo or ICI-target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI-target-chemo.
背景
免疫检查点抑制剂（ICI）联合治疗为不可切除的肝内胆管癌（uICC）的治疗提供了新的选择。
目的
比较不同抗 PD-1 联合治疗作为 uICC 一线治疗的效果。
方法
本研究纳入了 318 例来自中国 22 个中心的患者，他们接受了单独化疗（Chemo）、抗 PD-1 联合化疗（ICI-chemo）、抗 PD-1 联合靶向治疗（ICI-target）或抗 PD-1 联合靶向治疗和化疗（ICI-target-chemo）作为 uICC 的一线治疗。主要终点是无进展生存期（PFS）。次要终点包括总生存期（OS）、客观缓解率（ORR）和安全性。
结果
ICI-chemo（mPFS，6.3 个月；HR：0.61，95%CI：0.42-0.88；p=0.008；mOS，10.7 个月；HR：0.61，95%CI：0.39-0.94；p=0.026）、ICI-target（7.2 个月；HR：0.54，95%CI：0.36-0.80；p=0.002；15.8 个月；HR：0.54，95%CI：0.35-0.84；p=0.006）或 ICI-target-chemo（6.9 个月；HR：0.65，95%CI：0.47-0.90；p=0.009；14.4 个月；HR：0.47，95%CI：0.31-0.70；p<0.001）的临床结局优于 Chemo（3.8 个月；9.3 个月）。ICI-target 在生存结局方面并不逊于 ICI-chemo（HR for PFS：0.88，95%CI：0.55-1.42；p=0.614；HR for OS：0.89，95%CI：0.51-1.55；p=0.680）。ICI-target-chemo 的预后与 ICI-chemo（HR for PFS：1.07，95%CI：0.70-1.62；p=0.764；HR for OS：0.77，95%CI：0.45-1.31；p=0.328）和 ICI-target（HR for PFS：1.20，95%CI：0.77-1.88；p=0.413；HR for OS：0.86，95%CI：0.51-1.47；p=0.583）相似，但不良反应更多（p<0.001；p=0.010）。多变量和倾向评分分析支持这些发现。
结论
在 uICC 患者中，ICI-chemo 或 ICI-target 与 Chemo 相比提供了更多的生存获益，同时与 ICI-target-chemo 相比，实现了相当的预后且不良反应更少。
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