PD-1/PD-L1抑制剂在非小细胞肺癌肝转移患者中的疗效：一项真实世界研究
The Efficacy of PD-1/PD-L1 Inhibitors in Patients with Liver Metastasis of Non-Small Cell Lung Cancer: A Real-World Study.
作者信息
Xie Mingying, Li Na, Xu Xiaoling, Xu Yanjun, Li Hui, Zhu Liang, Sheng Jiamin, Zhou Zichao, Fan Yun
机构信息
Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Department of Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China.
出版信息
Cancers (Basel). 2022 Sep 5;14(17):4333. doi: 10.3390/cancers14174333.
BACKGROUND
A controversy exists regarding the efficacy of programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) inhibitors for patients with non-small cell lung cancer (NSCLC) and liver metastases. Our study retrospectively evaluated the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients with liver metastases.
METHODS
This retrospective study included 1627 lung cancer patients who received immunotherapy. Among 648 patients who had advanced NSCLC and received PD-1/PD-L1 inhibitors, 61 had liver metastases and 587 did not have. We analyzed patient characteristics, progression-free survival (PFS) and overall survival (OS). An exploratory analysis of biomarkers including CD4, CD8 and CD68 for efficacy in patients with liver metastases was also performed.
RESULTS
In liver metastasis patients receiving PD-1/PD-L1 inhibitors, the objective response rate (ORR) was 29.5%, the disease control rate (DCR) was 72.1%, PFS was 6.4 months and OS was 15.2 months, which were all worse than those of patients without liver metastases (ORR: 35.8%; DCR: 81.8%; PFS: 7.9 months, = 0.001; OS: 20.6 months, = 0.008). When compared to non-liver lesions, the ORR (26.2 vs. 39.3%) and DCR (75.4 vs. 88.5%) of liver lesions were lower. During the analysis of PD-L1 expression, 27 PD-L1-positive patients had a longer PFS than 21 patients in the negative group ( = 0.012). Being PD-L1 positive was the independent prognostic indicators for PFS ( = 0.006). Additionally, the PD-L1 and CD8 dual-positive group responded favorably to PD-1/PD-L1 inhibitors.
CONCLUSIONS
PD-1/PD-L1 inhibitors are effective in liver metastasis-NSCLC patients. However, the efficacy is inferior when compared to those of patients without liver metastases. In NSCLC patients with liver metastases, PD-L1 expression and CD8+ T cell infiltration can predict the response of PD-1/PD-L1-directed immunotherapy.
背景
程序性死亡受体 1（PD-1）/程序性死亡配体 1（PD-L1）抑制剂对非小细胞肺癌（NSCLC）合并肝转移患者的疗效存在争议。我们的研究回顾性评估了 PD-1/PD-L1 抑制剂在 NSCLC 合并肝转移患者中的疗效。
方法
这项回顾性研究纳入了 1627 例接受免疫治疗的肺癌患者。在 648 例晚期 NSCLC 且接受 PD-1/PD-L1 抑制剂治疗的患者中，61 例有肝转移，587 例无肝转移。我们分析了患者特征、无进展生存期（PFS）和总生存期（OS）。还对包括 CD4、CD8 和 CD68 在内的生物标志物进行了探索性分析，以评估其在肝转移患者中的疗效。
结果
在接受 PD-1/PD-L1 抑制剂治疗的肝转移患者中，客观缓解率（ORR）为 29.5%，疾病控制率（DCR）为 72.1%，PFS 为 6.4 个月，OS 为 15.2 个月，均低于无肝转移患者（ORR：35.8%；DCR：81.8%；PFS：7.9 个月，P = 0.001；OS：20.6 个月，P = 0.008）。与非肝脏病灶相比，肝脏病灶的 ORR（26.2%对 39.3%）和 DCR（75.4%对 88.5%）较低。在分析 PD-L1 表达时，27 例 PD-L1 阳性患者的 PFS 长于 21 例阴性组患者（P = 0.012）。PD-L1 阳性是 PFS 的独立预后指标（P = 0.006）。此外，PD-L1 和 CD8 双阳性组对 PD-1/PD-L1 抑制剂反应良好。
结论
PD-1/PD-L1 抑制剂对 NSCLC 肝转移患者有效。然而，与无肝转移患者相比，疗效较差。在 NSCLC 肝转移患者中，PD-L1 表达和 CD8 + T 细胞浸润可预测 PD-1/PD-L1 导向免疫治疗的反应。
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