Objectives

Combination therapy of immune checkpoint inhibitors and chemotherapy is considered to be one of the standard treatment options for patients with advanced non-small-cell lung cancer (NSCLC). However, the clinical significance of immune checkpoint inhibitors combined with chemotherapy in elderly patients with NSCLC has not yet been fully understood. Therefore, this study aimed to evaluate how aging affects the therapeutic impact of chemotherapy combine with immune checkpoint inhibitors in elderly patients.

Materials and methods

We retrospectively analyzed 203 patients with advanced NSCLC who were treated with the combination therapy of pembrolizumab and chemotherapy between January 2019 and December 2019 at 12 institutions in Japan. We analyzed the clinical impacts of age on the following two groups: those who received pembrolizumab with platinum and pemetrexed (pemetrexed regimen) and those who received pembrolizumab with carboplatin and nab-paclitaxel/paclitaxel (paclitaxel regimen). Progression-free and overall survival were assessed via the Kaplan-Meier method.

Results

Multivariate analysis demonstrated that progression-free and overall survival were significantly shorter in elderly patients (aged ≥75 years) with NSCLC than in non-elderly patients (aged <75 years) with NSCLC in the pemetrexed regimen group. In contrast, there were no significant differences in progression-free and overall survival between elderly patients and non-elderly patients with NSCLC in the paclitaxel regimen group. In elderly patients with NSCLC, a programmed death-ligand 1 tumor proportion score of ≥50% was significantly associated with progression-free survival, and performance status of ≥2 was significantly associated with overall survival. Low albumin level (<3.5 g/dL) was significantly associated with both progression-free and overall survival.

Conclusion

The results of this retrospective study show that the pemetrexed regimen, but not the paclitaxel regimen, was related to poor clinical outcomes in elderly patients with NSCLC.

中文翻译：

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派姆单抗联合化疗对老年晚期非小细胞肺癌患者的临床影响

目标

免疫检查点抑制剂联合化疗被认为是晚期非小细胞肺癌（NSCLC）患者的标准治疗选择之一。然而，免疫检查点抑制剂联合化疗对老年NSCLC患者的临床意义尚不完全清楚。因此，本研究旨在评估衰老如何影响化疗联合免疫检查点抑制剂对老年患者的治疗效果。

材料和方法

我们回顾性分析了 2019 年 1 月至 2019 年 12 月在日本 12 家机构接受帕博利珠单抗联合化疗的 203 例晚期 NSCLC 患者。我们分析了年龄对以下两组的临床影响：接受帕博利珠单抗联合铂和培美曲塞（培美曲塞方案）和接受帕博利珠单抗联合卡铂和白蛋白结合型紫杉醇/紫杉醇（紫杉醇方案）的患者。通过 Kaplan-Meier 方法评估无进展生存期和总生存期。

结果

多变量分析表明，在培美曲塞方案组中，老年NSCLC患者（年龄≥75岁）的无进展生存期和总生存期明显短于非老年NSCLC患者（年龄<75岁）。相比之下，紫杉醇方案组老年NSCLC患者和非老年NSCLC患者的无进展生存期和总生存期没有显着差异。在老年NSCLC患者中，程序性死亡配体1肿瘤比例评分≥50%与无进展生存显着相关，体能状态≥2与总生存显着相关。低白蛋白水平 (<3.5 g/dL) 与无进展生存期和总生存期显着相关。

结论

这项回顾性研究的结果表明，培美曲塞方案，而不是紫杉醇方案，与老年 NSCLC 患者的不良临床结局有关。