Current Status and Prospect of PD-1/PD-L1 Immune Checkpoint Inhibitor Therapy in Elderly Patients with Advanced NSCLC

TL;DR

This paper reviews how PD-1/PD-L1 immune checkpoint inhibitors work in elderly patients with advanced non-small cell lung cancer, focusing on treatment benefits and risks.

Contribution

The paper provides a comprehensive analysis of current evidence and future directions for immune checkpoint inhibitor therapy in elderly NSCLC patients.

Findings

ICIs show similar benefits in patients aged 65-75 as in younger patients, but not in those over 75.

Immune-related adverse events are more severe in patients over 75.

Combining ICIs with low-intensity chemotherapy may be a promising option for elderly patients.

Abstract

癌症发病率与年龄密切相关，75%的非小细胞肺癌（non-small cell lung cancer, NSCLC）患者年龄均≥65岁。免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）的出现改变了NSCLC的治疗格局。针对老年患者有限的研究发现对于65-75岁的患者，ICIs单药显示出良好的获益，与年轻患者无明显差异，这种获益在免疫联合化疗或放疗中也有所体现。但是对于≥75岁的患者来说生存获益不明显。ICIs单药在不同年龄段的患者中免疫相关不良反应（immune-related adverse events, irAEs）发生率相似，免疫联合化疗对比单纯化疗导致irAEs的发生率高，≥75岁患者发生更高级别irAEs的可能性更大。除了老年患者免疫衰老会从多维度影响免疫微环境从而影响免疫治疗疗效外，东部肿瘤协作组体力状态（Eastern Cooperative Oncology Group performance status, ECOG PS）评分等也会影响预后。对于部分≥75岁或身体状况较差的患者，免疫联合低强度化疗成为有潜力的治疗方式之一，但相关研究较少，所以应有意识增加老年患者入组试验的人数，同时综合评估，探索个体化治疗方案。本综述拟对老年NSCLC患者应用抗程序性死亡受体1（programmed cell death protein 1, PD-1）及其配体（programmed cell death ligand 1, PD-L1）的相关研究进行汇总分析，以期为老年NSCLC患者的免疫治疗提供更多参考和指导，并结合其特点提出新的治疗展望。

Characteristics of immunosenescence

OS or PFS by age in randomized clinical trials of immunotherapy for advanced NSCLC