Wu Yingcheng, Ju Qianqian, Qian Bei, Zhang Feng, Shi Hui
Medical School of Nantong University, Jiangsu 226001, China.
Laboratory Animal Center of Nantong University, Jiangsu 226001, China.
Oncotarget. 2017 Dec 26;9(8):7942-7948. doi: 10.18632/oncotarget.23678. eCollection 2018 Jan 30.
Immunosenescence, the age-related decline of immunity, affects the immune responses of non-small cell lung cancer (NSCLC) patients. Through immune responses, programmed death-1 (PD-1) inhibitors exert their antitumor robustness. In different ages of NSCLC patients, especially the older patients, the effectiveness of PD-1 inhibitors remains unclear. It is still controversial whether pembrolizumab or nivolumab should be used in treating NSCLC patients.
2,192 NSCLC patients from four phase III RCTs were included. PD-1 inhibitors significantly prolonged the OS in both younger group (<65-year-age) (HR: 0.64, 95% CI: 0.54-0.75, = 0.000) and older group (≥65-year-age) (HR: 0.68, 95% CI: 0.54-0.81, = 0.001) than chemotherapy. Among patients aged over 75, no significantly longer OS was observed (HR: 1.02, 95% CI: 0.35-1.69, = 0.971) than controls. In the older group (≥65-year-age), HR of OS favors nivolumab rather than pembrolizumab.
Among patients aged over 75, no significantly prolonged overall survival was observed compared with chemotherapy. In comparison with pembrolizumab, nivolumab was associated with better OS in older NSCLC patients (≥65-year-age), and better PFS in all NSCLC patients. Older patients, especially those aged over 75, should be paid more attention to in the future clinical trials, guidelines, and clinical practice.
The authors included clinical trials testing PD-1 inhibitors (nivolumab and pembrolizumab) compared with chemotherapies in older and younger patients. The authors used the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS).
免疫衰老，即与年龄相关的免疫力下降，会影响非小细胞肺癌（NSCLC）患者的免疫反应。程序性死亡受体1（PD-1）抑制剂通过免疫反应发挥其抗肿瘤作用。在不同年龄段的NSCLC患者中，尤其是老年患者，PD-1抑制剂的疗效尚不清楚。派姆单抗或纳武单抗是否应用于治疗NSCLC患者仍存在争议。
纳入了来自四项III期随机对照试验（RCT）的2192例NSCLC患者。与化疗相比，PD-1抑制剂显著延长了较年轻组（<65岁）（风险比：0.64，95%置信区间：0.54-0.75，P<0.000）和较年长组（≥65岁）（风险比：0.68，95%置信区间：0.54-0.81，P = 0.001）的总生存期（OS）。在75岁以上的患者中，未观察到OS比对照组显著延长（风险比：1.02，95%置信区间：0.35-1.69，P = 0.971）。在较年长组（≥65岁）中，OS的风险比显示纳武单抗优于派姆单抗。
与化疗相比，在75岁以上的患者中未观察到总生存期显著延长。与派姆单抗相比，纳武单抗在老年NSCLC患者（≥65岁）中与更好的OS相关，在所有NSCLC患者中与更好的无进展生存期（PFS）相关。在未来的临床试验、指南和临床实践中，应更多地关注老年患者，尤其是75岁以上的患者。
作者纳入了比较PD-1抑制剂（纳武单抗和派姆单抗）与化疗在老年和年轻患者中的临床试验。作者使用了总生存期（OS）和无进展生存期（PFS）的风险比（HR）和95%置信区间（CI）。
