Objectives

Immune checkpoint inhibition after radiochemotherapy (RTCT) has become a new standard of care for locally advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression. However, little is known about the prognostic role of immune response markers in this setting. We analysed PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in tumour biopsies from the multicenter German Intergroup Lung Trial (GILT), which previously randomised patients with stage III NSCLC to RTCT with or without consolidation chemotherapy.

Materials and methods

We retrospectively analyzed tumour biopsies from patients treated in the GILT trial. PD-L1 expression was analysed using the Ventana SP263 assay and TiL score (low, intermediate, high) and pattern (excluded, inflamed, desert) were assessed. The primary endpoint of the biomarker analysis was PFS in patients with PD-L1 ≥ 1% vs. PD-L1 < 1% NSCLC. Secondary endpoints explored the prognostic relevance of additional PD-L1 expression levels and TiL score and pattern.

Results

Biopsies were available from 92 patients treated with RTCT. Patients with available tumor tissue did not differ significantly from the whole study population. PD-L1 scores from 78 samples were available for analysis. There was no difference in PFS in the PD-L1 < 1% vs. PD-L1 ≥ 1% subgroups. TiL score was available in 66 patients. Patients with high TiL score showed favourable overall survival compared to the low TiL subgroup. This trend was most pronounced in those patients treated with consolidative chemotherapy.

Conclusion

In this analysis, PD-L1 expression did not correlate with PFS following RTCT. However, patients with TiLs > 10% were found to have longer overall survival, especially for those patients treated with consolidation chemotherapy after the end of RTCT. Further analyses to explore the prognostic and predictive relevance of TiLs in the context of consolidative checkpoint inhibition with durvalumab are required.

中文翻译：

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在随机、多中心、III 期德国组间肺试验 (GILT) 中同时放化疗治疗的局部晚期 NSCLC 中 PD-L1 表达和肿瘤浸润淋巴细胞 (TiLs) 的预后和预测价值

目标

放化疗后免疫检查点抑制 (RTCT) 已成为程序性死亡配体 1 (PD-L1) 表达的局部晚期非小细胞肺癌的新护理标准。然而，关于免疫反应标志物在这种情况下的预后作用知之甚少。我们分析了来自多中心德国组间肺试验 (GILT) 的肿瘤活检组织中的 PD-L1 表达和肿瘤浸润淋巴细胞 (TiL)，该试验先前将 III 期 NSCLC 患者随机分配至 RTCT，伴或不伴巩固化疗。

材料和方法

我们回顾性分析了 GILT 试验中接受治疗的患者的肿瘤活检。使用 Ventana SP263 测定分析 PD-L1 表达，并评估 TiL 评分（低、中、高）和模式（排除、发炎、沙漠）。生物标志物分析的主要终点是 PD-L1 ≥ 1% 与 PD-L1 < 1% NSCLC 患者的 PFS。次要终点探讨了额外 PD-L1 表达水平和 TiL 评分和模式的预后相关性。

结果

92 名接受 RTCT 治疗的患者进行了活检。具有可用肿瘤组织的患者与整个研究人群没有显着差异。来自 78 个样本的 PD-L1 分数可用于分析。PD-L1 < 1% 与 PD-L1 ≥ 1% 亚组的 PFS 没有差异。66 名患者可获得 TiL 评分。与低 TiL 亚组相比，具有高 TiL 评分的患者显示出良好的总生存率。这种趋势在接受巩固化疗的患者中最为明显。

结论

在该分析中，PD-L1 表达与 RTCT 后的 PFS 无关。然而，发现 TiLs > 10% 的患者具有更长的总生存期，尤其是对于那些在 RTCT 结束后接受巩固化疗的患者。需要进一步分析以探索在使用 durvalumab 进行巩固检查点抑制的背景下 TiL 的预后和预测相关性。